1264:
412:
511:
1369:, which developed it. The failure of these drugs has been due largely to toxicity (in particular, musculo-skeletal toxicity in the case of broad spectrum inhibitors) and failure to show expected results (in the case of trocade, promising results in rabbit arthritis models were not replicated in human trials). The reasons behind the largely disappointing clinical results of MMP inhibitors is unclear, especially in light of their activity in
2809:
635:, and these enzymes are distinguished by the presence of an additional domain inserted into the catalytic domain. This gelatin-binding region is positioned immediately before the zinc-binding motif, and forms a separate folding unit that does not disrupt the structure of the catalytic domain. The gelatinases are No. 2 and No. 9.
1254:
is thought to be important in rheumatoid arthritis and osteoarthritis. Recent data suggests active role of MMPs in the pathogenesis of Aortic
Aneurysm. Excess MMPs degrade the structural proteins of the aortic wall. Disregulation of the balance between MMPs and TIMPs is also a characteristic of
479:
In the third mechanism, the
Manzetti-mechanism, Manzetti Sergio and colleagues provided evidence that a coordination between water and zinc during catalysis was unlikely, and suggested a third mechanism wherein a histidine from the HExxHxxGxxH-motif participates in
2066:
Synergistic effect of stromelysin-1 (matrix metalloproteinase-3) promoter (-1171 5A->6A) polymorphism in oral submucous fibrosis and head and neck lesions.Chaudhary AK, Singh M, Bharti AC, Singh M, Shukla S, Singh AK, Mehrotra R. BMC Cancer. 2010 Jul 14;10:369.
1271:
All MMPs are synthesized in the latent form (Zymogen). They are secreted as proenzymes and require extracellular activation. They can be activated in vitro by many mechanisms including organomercurials, chaotropic agents, and other proteases.
1338:, at subantimicrobial doses, inhibits MMP activity, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. It is used clinically for the treatment of
492:
ion is coordinated with the two oxygen atoms from the catalytic glutamic acid, the substrate's carbonyl oxygen atom, and the two histidine residues, and can polarize the glutamic acid's oxygen atom, proximate the
835:
MMP-11 shows more similarity to the MT-MMPs, is convertase-activatable and is secreted therefore usually associated to convertase-activatable MMPs. Substrates include Col IV, fibronectin, laminin, aggrecan
1326:
of the zinc atom. Other substituents of these inhibitors are usually designed to interact with various binding pockets on the MMP of interest, making the inhibitor more or less specific for given MMPs.
1349:
A number of rationally designed MMP inhibitors have shown some promise in the treatment of pathologies that MMPs are suspected to be involved in (see above). However, most of these, such as
620:, the current list of collagenases includes No. 1, No. 2, No. 8, No. 9, and No. 13. Collagenase No. 14 is present in MeSH but not listed as a collagenase, while No. 18 is absent from MeSH.
1777:"Cysteine array matrix metalloproteinase (CA-MMP)/MMP-23 is a type II transmembrane matrix metalloproteinase regulated by a single cleavage for both secretion and activation"
657:
However, it is becoming increasingly clear that these divisions are somewhat artificial as there are a number of MMPs that do not fit into any of the traditional groups.
561:
Analysis of the catalytic domains in isolation suggests that the catalytic domains evolved further once the major groups had differentiated, as is also indicated by the
577:
The most commonly used groupings (by researchers in MMP biology) are based partly on historical assessment of the substrate specificity of the MMP and partly on the
139:
1718:"The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family"
1927:
Manzetti S, McCulloch DR, Herington AC, van der Spoel D (2003). "Modeling of enzyme-substrate complexes for the metalloproteases MMP-3, ADAM-9 and ADAM-10".
1892:
Kester WR, Matthews BW (1977). "Crystallographic study of the binding of dipeptide inhibitors to thermolysin: implications for the mechanism of catalysis".
329:
PRCGxPD. Some MMPs have a prohormone convertase cleavage site (Furin-like) as part of this domain, which, when cleaved, activates the enzyme. MMP-23A and
237:
247:
degradation) during tadpole tail metamorphosis (by placing a tadpole tail in a collagen matrix plate). Therefore, the enzyme was named interstitial
1388:
1474:
642:
proteins but are unable to cleave the triple-helical fibrillar collagens. The three canonical members of this group are No. 3, No. 10, and No. 11.
461:
In the first mechanism, Browner M.F. and colleagues proposed the base-catalysis mechanism, carried out by the conserved glutamate residue and the
2133:
612:
capable of degrading them. The collagenases are No. 1, No. 8, No. 13, and No. 18. In addition, No. 14 has also been shown to cleave fibrillar
1343:
2096:
759:
membrane associated through binding to cholesterol sulfate in cell membranes, substrates include: fibronectin, laminin, Col IV, gelatin
429:. It has a four-bladed β-propeller structure. β-Propeller structures provide a large flat surface that is thought to be involved in
2414:
1037:
2153:
2086:
1413:
1281:
468:
In the second mechanism, the
Matthews-mechanism, Kester and Matthews suggested an interaction between a water molecule and the
434:
2475:
1206:
Matrix metalloproteinases combines with the metal binding protein, metallothionine; thus helping in metal binding mechanism.
1342:
and is the only MMP inhibitor that is widely available clinically. It is sold under the trade name
Periostat by the company
1980:"Epilysin, a novel human matrix metalloproteinase (MMP-28) expressed in testis and keratinocytes and in response to injury"
1646:
Eisen A, Jeffrey J, Gross J (1968). "Human skin collagenase. Isolation and mechanism of attack on the collagen molecule".
2162:
2126:
501:. At this stage, a water molecule acts on the dissociated scissile bond and completes the hydrolyzation of the substrate.
581:
of the MMP. These groups are the collagenases, the gelatinases, the stromelysins, and the membrane-type MMPs (MT-MMPs).
2829:
1488:"Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation"
2528:
360:
is a 20 Ă… (2 nm) groove that runs across the catalytic domain. In the part of the catalytic domain forming the
1857:
Browner MF, Smith WW, Castelhano AL (1995). "Matrilysin-inhibitor complexes: common themes among metalloproteases".
430:
348:
structures of several MMP catalytic domains have shown that this domain is an oblate sphere measuring 35 x 30 x 30
399:
The catalytic domain is connected to the C-terminal domain by a flexible hinge or linker region. This is up to 75
2119:
2684:
17:
2480:
1382:
1285:
1319:. Hydroxymates are particularly potent inhibitors of MMPs and other zinc-dependent enzymes, due to their
2799:
2374:
2369:
2785:
2772:
2759:
2746:
2733:
2720:
2707:
2669:
2101:
1393:
372:
residues found in the conserved sequence HExxHxxGxxH. Hence, this sequence is a zinc-binding motif.
2839:
2679:
2633:
2576:
2490:
2150:
2105:
617:
318:
186:
2581:
1168:. Unlike other MMPs this enzyme is constitutivley expressed in many tissues (Highly expressed in
217:
154:
488:
ion to assume a quasi-penta coordinated state, via its dissociation from it. In this state, the
2111:
305:
is active. The pro-peptide domain is part of the "cysteine switch." This contains a conserved
2844:
2602:
2521:
2465:
2076:
1346:. Minocycline, another tetracycline antibiotic, has also been shown to inhibit MMP activity.
562:
345:
334:
2674:
2146:
2021:"Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors"
1936:
1818:"Peptide ligands for the fibronectin type II modules of matrix metalloproteinase 2 (MMP-2)"
1729:
1600:
1541:
639:
146:
8:
2638:
1948:
1339:
258:
Later, it was purified from human skin (1968), and was recognized to be synthesized as a
150:
78:
1940:
1733:
1604:
1545:
2834:
2571:
1960:
1421:
578:
326:
174:
1623:
1588:
1564:
1529:
2077:
MBInfo – Matrix metalloproteinases (MMPs) facilitate extracellular matrix disassembly
2052:
2001:
1952:
1909:
1874:
1839:
1798:
1757:
1752:
1717:
1698:
1663:
1659:
1628:
1569:
1510:
1437:
1215:
433:. This determines substrate specificity and is the site for interaction with TIMP's (
274:
107:
1964:
1445:
593:
into distinctive 3/4 and 1/4 fragments. These collagens are the major components of
212:
and plants. They are distinguished from other endopeptidases by their dependence on
2617:
2612:
2586:
2514:
2042:
2032:
1991:
1944:
1901:
1866:
1829:
1788:
1747:
1737:
1690:
1655:
1618:
1608:
1559:
1549:
1500:
1492:
1429:
628:
498:
278:
173:
inactivation. MMPs are also thought to play a major role in cell behaviors such as
83:
59:
2664:
2648:
2561:
2170:
1366:
1316:
1308:
1181:
446:
220:, their ability to degrade extracellular matrix, and their specific evolutionary
71:
2813:
2702:
2643:
1362:
1193:
527:
473:
178:
1433:
2823:
2607:
2566:
1414:"Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs"
1227:
1219:
494:
209:
198:
182:
119:
1742:
510:
497:, and induce it to act as reversible electron donor. This forms an oxyanion
289:
domain, which is linked to the catalytic domain by a flexible hinge region.
2556:
2081:
2056:
2005:
1996:
1979:
1956:
1843:
1834:
1817:
1802:
1793:
1776:
1632:
1613:
1573:
1554:
1514:
1441:
1370:
1223:
1165:
1164:
Discovered in 2001 and given its name due to have been discovered in human
931:
type-I transmembrane MMP; substrates include gelatin, fibronectin, laminin
912:
type-I transmembrane MMP; substrates include gelatin, fibronectin, laminin
893:
type-I transmembrane MMP; substrates include gelatin, fibronectin, laminin
653:
cleavage site in the pro-peptide, which is a feature also shared by No. 11.
530:
methods to compare the primary sequences of the MMPs suggest the following
420:
321:, keeping the enzyme in an inactive form. In the majority of the MMPs, the
244:
233:
221:
190:
1878:
1761:
1702:
1667:
2780:
2715:
2551:
2485:
2470:
2315:
1913:
1681:
Harper E, Bloch K, Gross J (1971). "The zymogen of tadpole collagenase".
1365:. The failure of Marimastat was partially responsible for the folding of
1335:
1304:
1300:
586:
384:
361:
357:
314:
248:
205:
153:
molecules. They are known to be involved in the cleavage of cell surface
1905:
1870:
1694:
1505:
1487:
1263:
1218:
associated with various physiological or pathological processes such as
1200:, skin). A threonine replaces proline in its cysteine switch (PRCGVTD).
1101:
MMP-25, MMP20, MMP20A, MMPL1, MT-MMP 6, MT-MMP6, MT6-MMP, MT6MMP, MTMMP6
411:
2460:
2332:
1926:
1475:
1354:
1350:
1239:
1107:
976:
950:
710:
624:
400:
286:
282:
162:
127:
123:
2047:
2037:
2020:
1589:"Collagenolytic Activity in Amphibian Tissues: A Tissue Culture Assay"
1530:"Collagenolytic activity in amphibian tissues: a tissue culture assay"
2754:
2728:
1323:
1320:
1292:
1235:
1231:
1185:
598:
531:
481:
426:
369:
353:
213:
194:
166:
158:
2018:
616:, and there is evidence that No. 2 is capable of collagenolysis. In
2808:
2495:
2297:
2292:
2287:
2142:
1189:
778:
Substrates include Col I, II, III, VII, VIII, X, aggrecan, gelatin
613:
590:
442:
349:
322:
306:
298:
241:
170:
135:
66:
145:
Collectively, these enzymes are capable of degrading all kinds of
2282:
2277:
2272:
2267:
2262:
2257:
2252:
2097:
Currently identified substrates for mammalian MMPs at clip.ubc.ca
964:
887:
MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP, MTMMP1, WNCHRS
632:
423:
259:
131:
111:
2141:
1816:
Trexler M, Briknarová K, Gehrmann M, Llinás M, Patthy L (2003).
2767:
2537:
2419:
2247:
2242:
2237:
2232:
2227:
2222:
2217:
2212:
2190:
2185:
2180:
1815:
1197:
1169:
1055:
609:
606:
602:
566:
330:
302:
2741:
2444:
2439:
2434:
2429:
2424:
2409:
2404:
2399:
2394:
2389:
2384:
2379:
2364:
2359:
2207:
2202:
2197:
2175:
1312:
1177:
1150:
1132:
1115:
1093:
1074:
1019:
1001:
983:
936:
917:
898:
879:
860:
841:
821:
802:
650:
646:
542:
438:
2354:
2349:
2342:
2337:
2325:
2320:
1358:
1296:
1251:
1247:
1243:
1173:
874:
Substrates include Col I, II, III, IV, IX, X, XIV, gelatin
783:
764:
745:
726:
704:
685:
594:
552:
548:
489:
485:
469:
462:
388:
380:
365:
310:
252:
115:
53:
2506:
301:
with a pro-peptide domain that must be removed before the
1082:
MMP-24, MMP25, MT-MMP 5, MT-MMP5, MT5-MMP, MT5MMP, MTMMP5
816:
Substrates include Col IV, laminin, fibronectin, elastin
699:
Substrates include Col I, II, III, VII, VIII, X, gelatin
419:
The C-terminal domain has structural similarities to the
2091:
1385:, a peptide that can bind and stain MMP cleaved collagen
445:. The membrane-bound MMPs (MT-MMPs) are anchored to the
208:
in 1962, including humans, but have since been found in
1715:
721:
Substrates include
Gelatin, Col I, II, III, IV, Vii, X
514:
Functional classification of matrix metalloproteinases.
406:
1856:
2797:
649:, No. 15, No. 16, No. 17, No. 24, and No. 25) have a
415:
The hemopexin-like C-terminal domain of MMP9 PDB 1itv
277:. The three common domains are the pro-peptide, the
1977:
638:The stromelysins display a broad ability to cleave
387:type II modules inserted immediately before in the
740:Substrates include Col II, IV, IX, X, XI, gelatin
589:are capable of degrading triple-helical fibrillar
1645:
988:RASI-1, occasionally referred to as stromelysin-4
953:-attached; substrates include fibrinogen, fibrin
2821:
1680:
1389:Drug discovery and development of MMP inhibitors
855:Substrates include elastin, fibronectin, Col IV
457:There are three catalytic mechanisms published.
2019:Snoek-van Beurden PAM; Von den Hoff JW (2005).
1534:Proceedings of the National Academy of Sciences
1353:(BB-2516), a broad-spectrum MMP inhibitor, and
449:via a transmembrane or a GPI-anchoring domain.
297:The MMPs are initially synthesized as inactive
1891:
1485:
1361:selective inhibitor, have performed poorly in
1280:The MMPs are inhibited by specific endogenous
518:The MMPs can be subdivided in different ways.
27:Family of zinc-dependent metalloendopeptidases
2522:
2127:
2087:Extracellular proteolysis at fibrinolysis.org
1978:Lohi J, Wilson CL, Roby JD, Parks WC (2001).
265:The "cysteine switch" was described in 1990.
1586:
1527:
1479:
1411:
1405:
1255:acute and chronic cardiovascular diseases.
1250:are thought to be important in metastasis.
149:proteins, but also can process a number of
2529:
2515:
2134:
2120:
925:C8orf57, MMP-X2, MT-MMP2, MT-MMP3, MT3-MMP
437:). The hemopexin-like domain is absent in
240:in 1962, who observed enzymatic activity (
2104:at the U.S. National Library of Medicine
2046:
2036:
1995:
1833:
1792:
1774:
1751:
1741:
1622:
1612:
1563:
1553:
1504:
1303:tightly. Common chelating groups include
1291:Synthetic inhibitors generally contain a
1284:(TIMPs), which comprise a family of four
403:long, and has no determinable structure.
317:and prevents binding and cleavage of the
1262:
509:
410:
391:-binding motif in the catalytic domain.
134:. The MMPs belong to a larger family of
1528:Gross, J.; Lapiere, C. M. (June 1962).
906:MT2-MMP, MTMMP2, SMCP-2, MMP-15, MT2MMP
340:
14:
2822:
1716:Van Wart H, Birkedal-Hansen H (1990).
1486:Van Lint P, Libert C (December 2007).
1288:: TIMP-1, TIMP-2, TIMP-3, and TIMP-4.
1282:tissue inhibitor of metalloproteinases
797:Substrates include Gelatin, Col IV, V
452:
435:tissue inhibitor of metalloproteinases
2510:
2476:Pregnancy-associated plasma protein A
2115:
1470:
1468:
1466:
1158:EPILYSIN, MM28, MMP-25, MMP-28, MMP25
1069:type-II transmembrane cysteine array
1050:type-II transmembrane cysteine array
734:CHDS6, MMP-3, SL-1, STMY, STMY1, STR1
2082:The Matrix Metalloproteinase Protein
441:, MMP-23, MMP-26, and the plant and
407:The hemopexin-like C-terminal domain
376:
1214:The MMPs play an important role in
394:
364:there is a catalytically important
24:
1949:10.1023/B:JCAM.0000005765.13637.38
1463:
292:
25:
2856:
2070:
1412:Verma RP, Hansch C (March 2007).
505:
232:MMPs were described initially by
2807:
309:residue that interacts with the
2012:
1971:
1920:
1885:
1850:
1809:
1330:
944:MT4-MMP, MMP-17, MT4MMP, MTMMP4
788:Gelatinase-B, 92 kDa gelatinase
521:
1768:
1709:
1674:
1639:
1580:
1521:
605:, and MMPs are the only known
273:The MMPs have a common domain
13:
1:
1399:
1275:
1258:
1108:glycosyl phosphatidylinositol
951:glycosyl phosphatidylinositol
572:
368:ion, which is bound by three
204:They were first described in
2481:Bone morphogenetic protein 1
1775:Pei D, Kang T, Qi H (2000).
1660:10.1016/0005-2744(68)90010-7
1383:Collagen hybridizing peptide
645:All six membrane-type MMPs (
431:protein-protein interactions
268:
7:
2536:
1587:Gross J, Lapiere C (1962).
1376:
1209:
1063:MIFR, MIFR-1, MMP22, MMP23A
623:The main substrates of the
122:; other family members are
10:
2861:
846:Macrophage metalloelastase
791:CLG4B, GELB, MANDP2, MMP-9
227:
2830:Matrix metalloproteinases
2693:
2685:Michaelis–Menten kinetics
2657:
2626:
2595:
2544:
2453:
2308:Matrix metalloproteinases
2306:
2161:
2102:Matrix+metalloproteinases
1929:J. Comput.-Aided Mol. Des
1434:10.1016/j.bmc.2007.01.011
1394:Proteases in angiogenesis
1295:that binds the catalytic
1267:mutual activation of MMPs
1088:type-I transmembrane MMP
772:CLG1, HNC, MMP-8, PMNL-CL
92:Matrix metalloproteinases
77:
65:
52:
44:
39:
34:
2577:Diffusion-limited enzyme
2491:Insulin-degrading enzyme
2106:Medical Subject Headings
1120:Matrilysin-2, endometase
690:Interstitial collagenase
660:
534:groupings of the MMPs:
337:segment in this domain.
100:matrix metallopeptidases
35:Matrix metalloproteinase
1743:10.1073/pnas.87.14.5578
1172:and at lower levels in
563:substrate specificities
352:(3.5 Ă— 3 x 3
1997:10.1074/jbc.M001599200
1835:10.1074/jbc.M210116200
1794:10.1074/jbc.M006493200
1722:Proc Natl Acad Sci USA
1614:10.1073/pnas.48.6.1014
1593:Proc Natl Acad Sci USA
1555:10.1073/pnas.48.6.1014
1268:
963:Collagenase 4, xcol4,
769:Neutrophil collagenase
515:
416:
346:X-ray crystallographic
2670:Eadie–Hofstee diagram
2603:Allosteric regulation
2466:Procollagen peptidase
2147:metalloendopeptidases
1266:
579:cellular localization
513:
414:
161:ligands (such as the
140:metzincin superfamily
2680:Lineweaver–Burk plot
1648:Biochim Biophys Acta
868:CLG3, MANDP1, MMP-13
849:HME, ME, MME, MMP-12
753:MMP-7, MPSL1, PUMP-1
640:extracellular matrix
341:The catalytic domain
147:extracellular matrix
1990:(13): 10134–10144.
1941:2003JCAMD..17..551M
1906:10.1021/bi00630a030
1871:10.1021/bi00020a004
1734:1990PNAS...87.5578V
1695:10.1021/bi00792a008
1605:1962PNAS...48.1014G
1546:1962PNAS...48.1014G
1506:10.1189/jlb.0607338
1340:periodontal disease
1286:protease inhibitors
1104:membrane-associated
1085:membrane-associated
1066:membrane-associated
1047:membrane-associated
991:MMP18, RASI-1, CODA
947:membrane-associated
928:membrane-associated
909:membrane-associated
890:membrane-associated
474:acid-base catalysis
453:Catalytic mechanism
2639:Enzyme superfamily
2572:Enzyme promiscuity
1422:Bioorg. Med. Chem.
1269:
750:Matrilysin, PUMP 1
557:All the other MMPs
516:
417:
327:conserved sequence
325:residue is in the
175:cell proliferation
108:metalloproteinases
2795:
2794:
2504:
2503:
2038:10.2144/05381RV01
1357:(Ro 32-3555), an
1216:tissue remodeling
1204:
1203:
709:Gelatinase-A, 72
157:, the release of
98:), also known as
89:
88:
16:(Redirected from
2852:
2812:
2811:
2803:
2675:Hanes–Woolf plot
2618:Enzyme activator
2613:Enzyme inhibitor
2587:Enzyme catalysis
2531:
2524:
2517:
2508:
2507:
2171:Alpha secretases
2136:
2129:
2122:
2113:
2112:
2061:
2060:
2050:
2040:
2016:
2010:
2009:
1999:
1975:
1969:
1968:
1924:
1918:
1917:
1889:
1883:
1882:
1854:
1848:
1847:
1837:
1813:
1807:
1806:
1796:
1787:(43): 33988–97.
1772:
1766:
1765:
1755:
1745:
1713:
1707:
1706:
1678:
1672:
1671:
1643:
1637:
1636:
1626:
1616:
1584:
1578:
1577:
1567:
1557:
1525:
1519:
1518:
1508:
1493:J. Leukoc. Biol.
1483:
1477:
1472:
1461:
1460:
1458:
1456:
1450:
1444:. Archived from
1418:
1409:
1299:atom at the MMP
829:SL-3, ST3, STMY3
665:
664:
629:type IV collagen
545:, 15, 16, and 17
499:transition state
484:by allowing the
395:The hinge region
279:catalytic domain
32:
31:
21:
2860:
2859:
2855:
2854:
2853:
2851:
2850:
2849:
2840:Metalloproteins
2820:
2819:
2818:
2806:
2798:
2796:
2791:
2703:Oxidoreductases
2689:
2665:Enzyme kinetics
2653:
2649:List of enzymes
2622:
2591:
2562:Catalytic triad
2540:
2535:
2505:
2500:
2449:
2302:
2157:
2140:
2073:
2064:
2017:
2013:
1976:
1972:
1925:
1921:
1900:(11): 2506–16.
1890:
1886:
1865:(20): 6602–10.
1855:
1851:
1828:(14): 12241–6.
1814:
1810:
1773:
1769:
1728:(14): 5578–82.
1714:
1710:
1689:(16): 3035–41.
1679:
1675:
1644:
1640:
1585:
1581:
1526:
1522:
1484:
1480:
1473:
1464:
1454:
1452:
1448:
1416:
1410:
1406:
1402:
1379:
1367:British Biotech
1363:clinical trials
1333:
1293:chelating group
1278:
1261:
1212:
1194:salivary glands
975:No known human
663:
575:
524:
508:
472:ion during the
455:
447:plasma membrane
409:
397:
343:
295:
293:The pro-peptide
271:
238:Charles Lapiere
230:
187:differentiation
28:
23:
22:
15:
12:
11:
5:
2858:
2848:
2847:
2842:
2837:
2832:
2817:
2816:
2793:
2792:
2790:
2789:
2776:
2763:
2750:
2737:
2724:
2711:
2697:
2695:
2691:
2690:
2688:
2687:
2682:
2677:
2672:
2667:
2661:
2659:
2655:
2654:
2652:
2651:
2646:
2641:
2636:
2630:
2628:
2627:Classification
2624:
2623:
2621:
2620:
2615:
2610:
2605:
2599:
2597:
2593:
2592:
2590:
2589:
2584:
2579:
2574:
2569:
2564:
2559:
2554:
2548:
2546:
2542:
2541:
2534:
2533:
2526:
2519:
2511:
2502:
2501:
2499:
2498:
2493:
2488:
2483:
2478:
2473:
2468:
2463:
2457:
2455:
2451:
2450:
2448:
2447:
2442:
2437:
2432:
2427:
2422:
2417:
2412:
2407:
2402:
2397:
2392:
2387:
2382:
2377:
2372:
2367:
2362:
2357:
2352:
2347:
2346:
2345:
2340:
2330:
2329:
2328:
2323:
2312:
2310:
2304:
2303:
2301:
2300:
2295:
2290:
2285:
2280:
2275:
2270:
2265:
2260:
2255:
2250:
2245:
2240:
2235:
2230:
2225:
2220:
2215:
2210:
2205:
2200:
2195:
2194:
2193:
2188:
2183:
2178:
2167:
2165:
2159:
2158:
2139:
2138:
2131:
2124:
2116:
2110:
2109:
2099:
2094:
2089:
2084:
2079:
2072:
2071:External links
2069:
2063:
2062:
2011:
1970:
1919:
1884:
1849:
1808:
1767:
1708:
1673:
1638:
1599:(6): 1014–22.
1579:
1540:(6): 1014–22.
1520:
1499:(6): 1375–81.
1478:
1462:
1451:on 13 May 2015
1428:(6): 2223–68.
1403:
1401:
1398:
1397:
1396:
1391:
1386:
1378:
1375:
1332:
1329:
1277:
1274:
1260:
1257:
1211:
1208:
1202:
1201:
1162:
1159:
1156:
1153:
1147:
1146:
1144:
1141:
1138:
1135:
1129:
1128:
1126:
1123:
1121:
1118:
1112:
1111:
1105:
1102:
1099:
1096:
1090:
1089:
1086:
1083:
1080:
1077:
1071:
1070:
1067:
1064:
1061:
1058:
1052:
1051:
1048:
1045:
1043:
1040:
1034:
1033:
1031:
1028:
1025:
1022:
1016:
1015:
1013:
1010:
1007:
1004:
998:
997:
995:
992:
989:
986:
980:
979:
973:
970:
968:
961:
955:
954:
948:
945:
942:
939:
933:
932:
929:
926:
923:
920:
914:
913:
910:
907:
904:
901:
895:
894:
891:
888:
885:
882:
876:
875:
872:
869:
866:
863:
857:
856:
853:
850:
847:
844:
838:
837:
833:
830:
827:
824:
818:
817:
814:
811:
808:
805:
799:
798:
795:
792:
789:
786:
780:
779:
776:
773:
770:
767:
761:
760:
757:
754:
751:
748:
742:
741:
738:
735:
732:
729:
723:
722:
719:
716:
714:
707:
701:
700:
697:
694:
691:
688:
682:
681:
678:
675:
672:
669:
662:
659:
655:
654:
643:
636:
621:
574:
571:
559:
558:
555:
546:
539:
523:
520:
507:
506:Classification
504:
503:
502:
477:
466:
454:
451:
408:
405:
396:
393:
383:, incorporate
342:
339:
294:
291:
270:
267:
229:
226:
185:/dispersion),
120:endopeptidases
87:
86:
81:
75:
74:
69:
63:
62:
57:
50:
49:
46:
42:
41:
37:
36:
26:
9:
6:
4:
3:
2:
2857:
2846:
2843:
2841:
2838:
2836:
2833:
2831:
2828:
2827:
2825:
2815:
2810:
2805:
2804:
2801:
2787:
2783:
2782:
2777:
2774:
2770:
2769:
2764:
2761:
2757:
2756:
2751:
2748:
2744:
2743:
2738:
2735:
2731:
2730:
2725:
2722:
2718:
2717:
2712:
2709:
2705:
2704:
2699:
2698:
2696:
2692:
2686:
2683:
2681:
2678:
2676:
2673:
2671:
2668:
2666:
2663:
2662:
2660:
2656:
2650:
2647:
2645:
2644:Enzyme family
2642:
2640:
2637:
2635:
2632:
2631:
2629:
2625:
2619:
2616:
2614:
2611:
2609:
2608:Cooperativity
2606:
2604:
2601:
2600:
2598:
2594:
2588:
2585:
2583:
2580:
2578:
2575:
2573:
2570:
2568:
2567:Oxyanion hole
2565:
2563:
2560:
2558:
2555:
2553:
2550:
2549:
2547:
2543:
2539:
2532:
2527:
2525:
2520:
2518:
2513:
2512:
2509:
2497:
2494:
2492:
2489:
2487:
2484:
2482:
2479:
2477:
2474:
2472:
2469:
2467:
2464:
2462:
2459:
2458:
2456:
2452:
2446:
2443:
2441:
2438:
2436:
2433:
2431:
2428:
2426:
2423:
2421:
2418:
2416:
2413:
2411:
2408:
2406:
2403:
2401:
2398:
2396:
2393:
2391:
2388:
2386:
2383:
2381:
2378:
2376:
2373:
2371:
2368:
2366:
2363:
2361:
2358:
2356:
2353:
2351:
2348:
2344:
2341:
2339:
2336:
2335:
2334:
2331:
2327:
2324:
2322:
2319:
2318:
2317:
2314:
2313:
2311:
2309:
2305:
2299:
2296:
2294:
2291:
2289:
2286:
2284:
2281:
2279:
2276:
2274:
2271:
2269:
2266:
2264:
2261:
2259:
2256:
2254:
2251:
2249:
2246:
2244:
2241:
2239:
2236:
2234:
2231:
2229:
2226:
2224:
2221:
2219:
2216:
2214:
2211:
2209:
2206:
2204:
2201:
2199:
2196:
2192:
2189:
2187:
2184:
2182:
2179:
2177:
2174:
2173:
2172:
2169:
2168:
2166:
2164:
2163:ADAM proteins
2160:
2155:
2152:
2148:
2144:
2137:
2132:
2130:
2125:
2123:
2118:
2117:
2114:
2107:
2103:
2100:
2098:
2095:
2093:
2090:
2088:
2085:
2083:
2080:
2078:
2075:
2074:
2068:
2058:
2054:
2049:
2044:
2039:
2034:
2030:
2026:
2025:BioTechniques
2022:
2015:
2007:
2003:
1998:
1993:
1989:
1985:
1981:
1974:
1966:
1962:
1958:
1954:
1950:
1946:
1942:
1938:
1935:(9): 551–65.
1934:
1930:
1923:
1915:
1911:
1907:
1903:
1899:
1895:
1888:
1880:
1876:
1872:
1868:
1864:
1860:
1853:
1845:
1841:
1836:
1831:
1827:
1823:
1819:
1812:
1804:
1800:
1795:
1790:
1786:
1782:
1778:
1771:
1763:
1759:
1754:
1749:
1744:
1739:
1735:
1731:
1727:
1723:
1719:
1712:
1704:
1700:
1696:
1692:
1688:
1684:
1677:
1669:
1665:
1661:
1657:
1654:(3): 637–45.
1653:
1649:
1642:
1634:
1630:
1625:
1620:
1615:
1610:
1606:
1602:
1598:
1594:
1590:
1583:
1575:
1571:
1566:
1561:
1556:
1551:
1547:
1543:
1539:
1535:
1531:
1524:
1516:
1512:
1507:
1502:
1498:
1495:
1494:
1489:
1482:
1476:
1471:
1469:
1467:
1447:
1443:
1439:
1435:
1431:
1427:
1424:
1423:
1415:
1408:
1404:
1395:
1392:
1390:
1387:
1384:
1381:
1380:
1374:
1372:
1371:animal models
1368:
1364:
1360:
1356:
1352:
1347:
1345:
1341:
1337:
1328:
1325:
1322:
1318:
1314:
1310:
1306:
1302:
1298:
1294:
1289:
1287:
1283:
1273:
1265:
1256:
1253:
1249:
1245:
1241:
1237:
1233:
1229:
1228:tissue repair
1225:
1221:
1220:morphogenesis
1217:
1207:
1199:
1195:
1191:
1187:
1183:
1179:
1175:
1171:
1167:
1166:keratinocytes
1163:
1160:
1157:
1154:
1152:
1149:
1148:
1145:
1142:
1139:
1137:MMP-22, C-MMP
1136:
1134:
1131:
1130:
1127:
1124:
1122:
1119:
1117:
1114:
1113:
1109:
1106:
1103:
1100:
1097:
1095:
1092:
1091:
1087:
1084:
1081:
1078:
1076:
1073:
1072:
1068:
1065:
1062:
1059:
1057:
1054:
1053:
1049:
1046:
1044:
1041:
1039:
1036:
1035:
1032:
1029:
1026:
1023:
1021:
1018:
1017:
1014:
1011:
1009:AI2A2, MMP-20
1008:
1005:
1003:
1000:
999:
996:
993:
990:
987:
985:
982:
981:
978:
974:
971:
969:
966:
962:
960:
957:
956:
952:
949:
946:
943:
940:
938:
935:
934:
930:
927:
924:
921:
919:
916:
915:
911:
908:
905:
902:
900:
897:
896:
892:
889:
886:
883:
881:
878:
877:
873:
870:
867:
865:Collagenase 3
864:
862:
859:
858:
854:
851:
848:
845:
843:
840:
839:
834:
831:
828:
826:Stromelysin 3
825:
823:
820:
819:
815:
812:
809:
807:Stromelysin 2
806:
804:
801:
800:
796:
793:
790:
787:
785:
782:
781:
777:
774:
771:
768:
766:
763:
762:
758:
755:
752:
749:
747:
744:
743:
739:
736:
733:
731:Stromelysin 1
730:
728:
725:
724:
720:
717:
715:
712:
708:
706:
703:
702:
698:
695:
692:
689:
687:
684:
683:
679:
676:
673:
670:
667:
666:
658:
652:
648:
644:
641:
637:
634:
630:
626:
622:
619:
615:
611:
608:
604:
600:
596:
592:
588:
584:
583:
582:
580:
570:
568:
564:
556:
554:
550:
547:
544:
540:
537:
536:
535:
533:
529:
528:bioinformatic
519:
512:
500:
496:
495:scissile bond
491:
487:
483:
478:
475:
471:
467:
464:
460:
459:
458:
450:
448:
444:
440:
436:
432:
428:
425:
422:
413:
404:
402:
392:
390:
386:
382:
378:
373:
371:
367:
363:
359:
355:
351:
347:
338:
336:
335:transmembrane
332:
328:
324:
320:
316:
312:
308:
304:
300:
290:
288:
284:
280:
276:
266:
263:
261:
256:
254:
250:
246:
243:
239:
235:
225:
223:
219:
215:
211:
210:invertebrates
207:
202:
200:
196:
192:
188:
184:
180:
176:
172:
168:
164:
160:
156:
152:
148:
143:
141:
138:known as the
137:
133:
129:
125:
121:
117:
113:
109:
105:
101:
97:
93:
85:
82:
80:
76:
73:
70:
68:
64:
61:
58:
55:
51:
47:
43:
38:
33:
30:
19:
18:Stromelysin-3
2845:Zinc enzymes
2781:Translocases
2778:
2765:
2752:
2739:
2726:
2716:Transferases
2713:
2700:
2557:Binding site
2316:Collagenases
2307:
2092:peptide shop
2065:
2031:(1): 73–83.
2028:
2024:
2014:
1987:
1983:
1973:
1932:
1928:
1922:
1897:
1894:Biochemistry
1893:
1887:
1862:
1859:Biochemistry
1858:
1852:
1825:
1821:
1811:
1784:
1780:
1770:
1725:
1721:
1711:
1686:
1683:Biochemistry
1682:
1676:
1651:
1647:
1641:
1596:
1592:
1582:
1537:
1533:
1523:
1496:
1491:
1481:
1453:. Retrieved
1446:the original
1425:
1420:
1407:
1348:
1334:
1331:Pharmacology
1309:carboxylates
1305:hydroxamates
1290:
1279:
1270:
1224:angiogenesis
1213:
1205:
1027:MMP-21, HTX7
958:
680:Description
656:
587:collagenases
576:
560:
532:evolutionary
525:
522:Evolutionary
517:
456:
418:
398:
374:
344:
296:
272:
264:
257:
245:triple helix
234:Jerome Gross
231:
222:DNA sequence
203:
199:host defense
191:angiogenesis
144:
118:-containing
103:
99:
95:
91:
90:
29:
2552:Active site
2486:Lysostaphin
2471:Thermolysin
2333:Gelatinases
1984:J Biol Chem
1822:J Biol Chem
1781:J Biol Chem
1336:Doxycycline
1317:phosphinyls
1301:active site
967:collagenase
810:SL-2, STMY2
625:gelatinases
401:amino acids
385:Fibronectin
377:gelatinases
362:active site
358:active site
315:active site
249:collagenase
206:vertebrates
128:serralysins
124:adamalysins
114:-dependent
40:Identifiers
2824:Categories
2755:Isomerases
2729:Hydrolases
2596:Regulation
2461:Neprilysin
2048:2066/47379
1455:21 October
1400:References
1355:cipemastat
1351:marimastat
1344:CollaGenex
1276:Inhibitors
1259:Activation
1240:metastasis
1110:-attached
1006:Enamelysin
977:orthologue
713:gelatinase
573:Functional
379:, such as
333:include a
287:C-terminal
283:haemopexin
281:, and the
214:metal ions
163:FAS ligand
79:Membranome
2835:EC 3.4.24
2634:EC number
2143:Proteases
1324:chelation
1321:bidentate
1236:arthritis
1232:cirrhosis
1186:intestine
1180:, brain,
693:CLG, CLGN
607:mammalian
599:cartilage
591:collagens
541:MMPs 11,
482:catalysis
427:hemopexin
370:histidine
319:substrate
275:structure
269:Structure
218:cofactors
195:apoptosis
179:migration
167:chemokine
159:apoptotic
155:receptors
151:bioactive
136:proteases
110:that are
104:matrixins
72:IPR021190
2658:Kinetics
2582:Cofactor
2545:Activity
2496:ZMPSTE24
2298:ADAMTS13
2293:ADAMTS12
2288:ADAMTS10
2057:15679089
2006:11121398
1965:17453639
1957:14713188
1844:12486137
1803:10945999
1633:13902219
1574:13902219
1515:17709402
1442:17275314
1377:See also
1210:Function
1190:placenta
1161:secreted
1155:Epilysin
1030:secreted
1012:secreted
871:secreted
852:secreted
832:secreted
813:secreted
794:secreted
775:secreted
756:secreted
737:secreted
718:secreted
696:secreted
677:Location
614:collagen
443:nematode
323:cysteine
307:cysteine
299:zymogens
242:collagen
183:adhesion
171:cytokine
132:astacins
67:InterPro
2814:Biology
2768:Ligases
2538:Enzymes
2283:ADAMTS9
2278:ADAMTS8
2273:ADAMTS5
2268:ADAMTS4
2263:ADAMTS3
2258:ADAMTS2
2253:ADAMTS1
1937:Bibcode
1879:7756291
1762:2164689
1730:Bibcode
1703:4331330
1668:4967132
1601:Bibcode
1542:Bibcode
1098:MT6-MMP
1079:MT5-MMP
965:xenopus
941:MT4-MMP
922:MT3-MMP
903:MT2-MMP
884:MT1-MMP
674:Aliases
633:gelatin
610:enzymes
567:enzymes
565:of the
526:Use of
424:protein
356:). The
331:MMP-23B
313:in the
260:zymogen
228:History
165:), and
112:calcium
2800:Portal
2742:Lyases
2420:MMP23B
2415:MMP23A
2248:ADAM33
2243:ADAM28
2238:ADAM23
2233:ADAM22
2228:ADAM18
2223:ADAM15
2218:ADAM12
2213:ADAM11
2191:ADAM19
2186:ADAM17
2181:ADAM10
2154:3.4.24
2108:(MeSH)
2055:
2004:
1963:
1955:
1914:861218
1912:
1877:
1842:
1801:
1760:
1750:
1701:
1666:
1631:
1624:220898
1621:
1572:
1565:220898
1562:
1513:
1440:
1315:, and
1313:thiols
1238:, and
1198:uterus
1170:testis
1140:MMP-27
1056:MMP23B
1042:CA-MMP
1038:MMP23A
647:No. 14
603:dentin
538:MMP-19
303:enzyme
285:-like
197:, and
130:, and
106:, are
60:CL0126
45:Symbol
2694:Types
2454:Other
2445:MMP28
2440:MMP27
2435:MMP26
2430:MMP25
2425:MMP24
2410:MMP21
2405:MMP20
2400:MMP19
2395:MMP17
2390:MMP16
2385:MMP15
2380:MMP14
2375:MMP13
2370:MMP12
2365:MMP11
2360:MMP10
2208:ADAM8
2203:ADAM7
2198:ADAM2
2176:ADAM9
1961:S2CID
1753:54368
1449:(PDF)
1417:(PDF)
1359:MMP-1
1252:MMP-1
1248:MMP-9
1244:MMP-2
1182:colon
1178:heart
1151:MMP28
1133:MMP27
1116:MMP26
1094:MMP25
1075:MMP24
1024:X-MMP
1020:MMP21
1002:MMP20
984:MMP19
959:MMP18
937:MMP17
918:MMP16
899:MMP15
880:MMP14
861:MMP13
842:MMP12
822:MMP11
803:MMP10
661:Genes
651:furin
553:MMP-9
549:MMP-2
439:MMP-7
421:serum
381:MMP-2
253:MMP-1
2786:list
2779:EC7
2773:list
2766:EC6
2760:list
2753:EC5
2747:list
2740:EC4
2734:list
2727:EC3
2721:list
2714:EC2
2708:list
2701:EC1
2355:MMP7
2350:MMP3
2343:MMP9
2338:MMP2
2326:MMP8
2321:MMP1
2053:PMID
2002:PMID
1953:PMID
1910:PMID
1875:PMID
1840:PMID
1799:PMID
1758:PMID
1699:PMID
1664:PMID
1629:PMID
1570:PMID
1511:PMID
1457:2015
1438:PMID
1297:zinc
1246:and
1174:lung
784:MMP9
765:MMP8
746:MMP7
727:MMP3
705:MMP2
686:MMP1
671:Name
668:Gene
631:and
627:are
618:MeSH
601:and
595:bone
585:The
551:and
465:ion.
389:zinc
375:The
311:zinc
236:and
116:zinc
96:MMPs
56:clan
54:Pfam
2043:hdl
2033:doi
1992:doi
1988:276
1945:doi
1902:doi
1867:doi
1830:doi
1826:278
1789:doi
1785:275
1748:PMC
1738:doi
1691:doi
1656:doi
1652:151
1619:PMC
1609:doi
1560:PMC
1550:doi
1501:doi
1430:doi
711:kDa
255:).
216:as
102:or
84:317
48:MMP
2826::
2151:EC
2145::
2051:.
2041:.
2029:38
2027:.
2023:.
2000:.
1986:.
1982:.
1959:.
1951:.
1943:.
1933:17
1931:.
1908:.
1898:16
1896:.
1873:.
1863:34
1861:.
1838:.
1824:.
1820:.
1797:.
1783:.
1779:.
1756:.
1746:.
1736:.
1726:87
1724:.
1720:.
1697:.
1687:10
1685:.
1662:.
1650:.
1627:.
1617:.
1607:.
1597:48
1595:.
1591:.
1568:.
1558:.
1548:.
1538:48
1536:.
1532:.
1509:.
1497:82
1490:.
1465:^
1436:.
1426:15
1419:.
1373:.
1311:,
1307:,
1242:.
1234:,
1230:,
1226:,
1222:,
1196:,
1192:,
1188:,
1184:,
1176:,
597:,
569:.
543:14
490:Zn
486:Zn
470:Zn
463:Zn
366:Zn
354:nm
262:.
224:.
201:.
193:,
189:,
177:,
142:.
126:,
2802::
2788:)
2784:(
2775:)
2771:(
2762:)
2758:(
2749:)
2745:(
2736:)
2732:(
2723:)
2719:(
2710:)
2706:(
2530:e
2523:t
2516:v
2156:)
2149:(
2135:e
2128:t
2121:v
2059:.
2045::
2035::
2008:.
1994::
1967:.
1947::
1939::
1916:.
1904::
1881:.
1869::
1846:.
1832::
1805:.
1791::
1764:.
1740::
1732::
1705:.
1693::
1670:.
1658::
1635:.
1611::
1603::
1576:.
1552::
1544::
1517:.
1503::
1459:.
1432::
1143:–
1125:–
1060:–
994:–
972:–
476:.
350:Ă…
251:(
181:(
169:/
94:(
20:)
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