1722:
29:
571:
are histidine, glutamate, aspartate or lysine and at least one other residue is required for catalysis, which may play an electrophilic role. Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site. The
324:
166:
1046:
280:
268:
110:
98:
634:
1388:
838:
552:
Metalloproteases are the most diverse of the four main protease types, with more than 50 families classified to date. In these enzymes, a
1075:
1039:
983:
761:
King, John V.; Liang, Wenguang G.; Scherpelz, Kathryn P.; Schilling, Alexander B.; Meredith, Stephen C.; Tang, Wei-Jen (2014-07-08).
1441:
647:
Metalloproteinase inhibitors are found in numerous marine organisms, including fish, cephalopods, mollusks, algae and bacteria.
1032:
502:
peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C,
1597:
344:
186:
1393:
576:
is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often
1712:
1287:
1282:
1582:
1752:
1698:
1685:
1672:
1659:
1646:
1633:
1620:
1066:
614:
1592:
1546:
1489:
1403:
1220:
1063:
996:
671:
491:
473:
383:
which plays a significant role in the fusion of muscle cells during embryo development, in a process known as
332:
174:
1494:
541:
that characterises the clan or family may have lost its catalytic activity, yet retained its function in
1515:
1434:
1378:
618:
523:
1587:
328:
170:
1059:
875:
709:
483:
1551:
676:
638:
603:
592:
546:
469:
450:
122:
1757:
1747:
1742:
1484:
538:
1024:
954:
903:
844:
834:
800:
782:
743:
725:
319:
161:
1530:
1525:
1499:
1427:
1327:
992:
944:
934:
893:
883:
826:
790:
774:
733:
717:
449:
that removes zinc, which is essential for activity. They are also inhibited by the chelator
980:
698:"Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism"
530:. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated
311:
153:
1577:
1561:
1474:
1083:
987:
864:"Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp"
499:
438:
261:
91:
879:
763:"Molecular basis of substrate recognition and degradation by human presequence protease"
713:
1726:
1615:
1556:
949:
922:
898:
863:
795:
762:
738:
697:
630:
607:
446:
273:
103:
494:, and M16 metalloproteinases such as Insulin Degrading Enzyme and Presequence Protease
1736:
1520:
1479:
830:
696:
Shen, Yuequan; Joachimiak, Andrzej; Rosner, Marsha Rich; Tang, Wei-Jen (2006-10-19).
626:
573:
479:
1004:
224:
54:
1469:
487:
465:
307:
149:
285:
237:
127:
115:
67:
1020:
888:
249:
79:
1693:
1628:
1464:
1398:
1383:
1228:
659:
589:
581:
527:
519:
1721:
1373:
1245:
821:
Rawlings ND, Barrett AJ (1995). "Evolutionary families of metallopeptidases".
778:
585:
564:
515:
384:
786:
729:
1667:
1641:
514:; and U, unknown. The serine, threonine and cysteine peptidases utilise the
511:
419:
415:
411:
372:
958:
907:
804:
747:
939:
848:
28:
1408:
1210:
1205:
1200:
1055:
1016:
651:
641:
553:
534:
503:
427:
365:
244:
74:
721:
1195:
1190:
1185:
1180:
1175:
1170:
1165:
654:
sterol-regulatory element binding protein (SREBP) site 2 protease and
596:
568:
542:
403:
923:"Metalloproteinase inhibitors: status and scope from marine organisms"
1680:
1450:
1332:
1160:
1155:
1150:
1145:
1140:
1135:
1130:
1125:
1103:
1098:
1093:
976:
577:
556:
507:
431:
423:
407:
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368:
339:
256:
181:
86:
1654:
1357:
1352:
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1337:
1322:
1317:
1312:
1307:
1302:
1297:
1292:
1277:
1272:
1120:
1115:
1110:
1088:
600:
531:
376:
599:
is never found in this site, possibly because it would break the
1267:
1262:
1255:
1250:
1238:
1233:
1012:
622:
442:
391:
301:
231:
219:
143:
61:
49:
1423:
1028:
560:
399:
1419:
825:. Methods in Enzymology. Vol. 248. pp. 183–228.
559:, usually zinc, activates the water molecule. The metal
410:. The ligands coordinating the metal ion can vary with
1011:
This article incorporates text from the public domain
1710:
979:
online database for peptidases and their inhibitors:
823:
Proteolytic
Enzymes: Aspartic and Metallo Peptidases
650:
Members of the M50 metallopeptidase family include:
430:. The fourth coordination position is taken up by a
1606:
1570:
1539:
1508:
1457:
1366:
1219:
1074:
486:(3.4.24). Well known metalloendopeptidases include
338:
318:
300:
295:
279:
267:
255:
243:
230:
218:
210:
205:
200:
180:
160:
142:
137:
121:
109:
97:
85:
73:
60:
48:
40:
35:
21:
580:or threonine and forms part of the S1' subsite in
567:ligands, usually three in number. The known metal
633:1, which proteolytically removes the C-terminal
461:There are two subgroups of metalloproteinases:
1435:
1040:
816:
814:
8:
526:- these peptidases can also readily act as
1442:
1428:
1420:
1047:
1033:
1025:
445:leads to complete inactivation. EDTA is a
292:
134:
27:
995:at the U.S. National Library of Medicine
948:
938:
897:
887:
862:Minde DP, Maurice MM, RĂĽdiger SG (2012).
794:
737:
588:, 'b' is an uncharged residue, and 'c' a
1717:
688:
613:Metallopeptidases from family M48 are
197:
18:
1389:Pregnancy-associated plasma protein A
7:
537:. In many instances, the structural
927:Biochemistry Research International
506:; G, glutamic acid; M, metallo; S,
14:
1720:
390:Most metalloproteases require
1:
296:Available protein structures:
138:Available protein structures:
1394:Bone morphogenetic protein 1
889:10.1371/journal.pone.0046147
831:10.1016/0076-6879(95)48015-3
1774:
1010:
921:Thomas NV, Kim SK (2010).
615:integral membrane proteins
1598:Michaelis–Menten kinetics
1221:Matrix metalloproteinases
779:10.1016/j.str.2014.05.003
492:matrix metalloproteinases
291:
133:
26:
1490:Diffusion-limited enzyme
1404:Insulin-degrading enzyme
997:Medical Subject Headings
672:Matrix metalloproteinase
658:protease EcfE, stage IV
625:ion per subunit. These
621:and Golgi, binding one
402:is coordinated to the
1583:Eadie–Hofstee diagram
1516:Allosteric regulation
1379:Procollagen peptidase
1060:metalloendopeptidases
619:endoplasmic reticulum
610:in metalloproteases.
484:metalloendopeptidases
375:mechanism involves a
1593:Lineweaver–Burk plot
629:include CAAX prenyl
617:associated with the
563:is held in place by
470:metalloexopeptidases
940:10.1155/2010/845975
880:2012PLoSO...746147M
722:10.1038/nature05143
714:2006Natur.443..870S
677:The Proteolysis Map
451:orthophenanthroline
1552:Enzyme superfamily
1485:Enzyme promiscuity
986:2017-04-04 at the
981:Metallo Peptidases
1708:
1707:
1417:
1416:
840:978-0-12-182149-4
708:(7113): 870–874.
522:and form an acyl
379:. An example is
358:metalloproteinase
354:
353:
350:
349:
345:structure summary
196:
195:
192:
191:
187:structure summary
1765:
1753:Protein families
1725:
1724:
1716:
1588:Hanes–Woolf plot
1531:Enzyme activator
1526:Enzyme inhibitor
1500:Enzyme catalysis
1444:
1437:
1430:
1421:
1084:Alpha secretases
1049:
1042:
1035:
1026:
1005:Metalloproteases
993:Metalloproteases
963:
962:
952:
942:
918:
912:
911:
901:
891:
859:
853:
852:
818:
809:
808:
798:
758:
752:
751:
741:
693:
656:Escherichia coli
606:adopted by this
545:recognition and
439:chelating agents
434:water molecule.
293:
198:
135:
31:
19:
1773:
1772:
1768:
1767:
1766:
1764:
1763:
1762:
1733:
1732:
1731:
1719:
1711:
1709:
1704:
1616:Oxidoreductases
1602:
1578:Enzyme kinetics
1566:
1562:List of enzymes
1535:
1504:
1475:Catalytic triad
1453:
1448:
1418:
1413:
1362:
1215:
1070:
1053:
1023:
988:Wayback Machine
972:
967:
966:
920:
919:
915:
861:
860:
856:
841:
820:
819:
812:
773:(7): 996–1007.
760:
759:
755:
695:
694:
690:
685:
668:
500:MEROPS database
459:
437:Treatment with
394:, but some use
362:metalloprotease
269:OPM superfamily
99:OPM superfamily
17:
12:
11:
5:
1771:
1769:
1761:
1760:
1755:
1750:
1745:
1735:
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1689:
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1580:
1574:
1572:
1568:
1567:
1565:
1564:
1559:
1554:
1549:
1543:
1541:
1540:Classification
1537:
1536:
1534:
1533:
1528:
1523:
1518:
1512:
1510:
1506:
1505:
1503:
1502:
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1325:
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1315:
1310:
1305:
1300:
1295:
1290:
1285:
1280:
1275:
1270:
1265:
1260:
1259:
1258:
1253:
1243:
1242:
1241:
1236:
1225:
1223:
1217:
1216:
1214:
1213:
1208:
1203:
1198:
1193:
1188:
1183:
1178:
1173:
1168:
1163:
1158:
1153:
1148:
1143:
1138:
1133:
1128:
1123:
1118:
1113:
1108:
1107:
1106:
1101:
1096:
1091:
1080:
1078:
1072:
1071:
1054:
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1044:
1037:
1029:
1009:
1008:
1000:
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970:External links
968:
965:
964:
913:
874:(10): e46147.
854:
839:
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753:
687:
686:
684:
681:
680:
679:
674:
667:
664:
635:three residues
627:endopeptidases
496:
495:
480:Endopeptidases
477:
458:
457:Classification
455:
447:metal chelator
352:
351:
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347:
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16:Type of enzyme
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13:
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3:
2:
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1579:
1576:
1575:
1573:
1569:
1563:
1560:
1558:
1557:Enzyme family
1555:
1553:
1550:
1548:
1545:
1544:
1542:
1538:
1532:
1529:
1527:
1524:
1522:
1521:Cooperativity
1519:
1517:
1514:
1513:
1511:
1507:
1501:
1498:
1496:
1493:
1491:
1488:
1486:
1483:
1481:
1480:Oxyanion hole
1478:
1476:
1473:
1471:
1468:
1466:
1463:
1462:
1460:
1456:
1452:
1445:
1440:
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1426:
1425:
1422:
1410:
1407:
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1400:
1397:
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1227:
1226:
1224:
1222:
1218:
1212:
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1207:
1204:
1202:
1199:
1197:
1194:
1192:
1189:
1187:
1184:
1182:
1179:
1177:
1174:
1172:
1169:
1167:
1164:
1162:
1159:
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1134:
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1129:
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1100:
1097:
1095:
1092:
1090:
1087:
1086:
1085:
1082:
1081:
1079:
1077:
1076:ADAM proteins
1073:
1068:
1065:
1061:
1057:
1050:
1045:
1043:
1038:
1036:
1031:
1030:
1027:
1022:
1018:
1014:
1007:
1006:
1002:Proteopedia:
1001:
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994:
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989:
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873:
869:
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842:
836:
832:
828:
824:
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815:
811:
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802:
797:
792:
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784:
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768:
764:
757:
754:
749:
745:
740:
735:
731:
727:
723:
719:
715:
711:
707:
703:
699:
692:
689:
682:
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675:
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669:
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648:
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643:
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632:
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587:
583:
579:
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562:
558:
555:
550:
548:
544:
540:
536:
533:
529:
525:
521:
517:
513:
509:
505:
501:
493:
489:
488:ADAM proteins
485:
481:
478:
475:
471:
467:
466:Exopeptidases
464:
463:
462:
456:
454:
452:
448:
444:
440:
435:
433:
429:
425:
421:
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413:
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401:
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242:
239:
236:
233:
229:
226:
223:
221:
217:
214:Peptidase_M50
213:
209:
204:
201:Peptidase_M50
199:
188:
185:
183:
179:
176:
172:
168:
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63:
59:
56:
53:
51:
47:
44:Peptidase_M48
43:
39:
34:
30:
25:
22:Peptidase_M48
20:
1694:Translocases
1691:
1678:
1665:
1652:
1639:
1629:Transferases
1626:
1613:
1470:Binding site
1229:Collagenases
1003:
930:
926:
916:
871:
867:
857:
822:
770:
766:
756:
705:
701:
691:
662:protein FB.
655:
649:
646:
639:farnesylated
612:
551:
539:protein fold
528:transferases
524:intermediate
497:
460:
436:
398:. The metal
389:
361:
357:
355:
1465:Active site
1399:Lysostaphin
1384:Thermolysin
1246:Gelatinases
660:sporulation
590:hydrophobic
582:thermolysin
520:nucleophile
281:OPM protein
206:Identifiers
111:OPM protein
36:Identifiers
1737:Categories
1668:Isomerases
1642:Hydrolases
1509:Regulation
1374:Neprilysin
933:: 845975.
683:References
586:neprilysin
565:amino acid
516:amino acid
476:: 3.4.17).
406:via three
385:myogenesis
308:structures
150:structures
123:Membranome
1758:Proteases
1748:EC 3.4.17
1743:EC 3.4.24
1547:EC number
1056:Proteases
1021:IPR008915
787:1878-4186
767:Structure
730:1476-4687
652:mammalian
604:structure
512:threonine
474:EC number
420:aspartate
416:glutamate
412:histidine
373:catalytic
364:, is any
250:IPR008915
80:IPR001915
1571:Kinetics
1495:Cofactor
1458:Activity
1409:ZMPSTE24
1211:ADAMTS13
1206:ADAMTS12
1201:ADAMTS10
1017:InterPro
984:Archived
959:21197102
908:23056252
868:PLOS ONE
805:24931469
748:17051221
666:See also
642:proteins
631:protease
554:divalent
535:molecule
504:cysteine
441:such as
428:arginine
366:protease
325:RCSB PDB
245:InterPro
167:RCSB PDB
75:InterPro
1727:Biology
1681:Ligases
1451:Enzymes
1196:ADAMTS9
1191:ADAMTS8
1186:ADAMTS5
1181:ADAMTS4
1176:ADAMTS3
1171:ADAMTS2
1166:ADAMTS1
950:3004377
899:3463568
876:Bibcode
849:7674922
796:4128088
739:3366509
710:Bibcode
601:helical
597:Proline
593:residue
569:ligands
547:binding
543:protein
498:In the
408:ligands
404:protein
225:PF02163
55:PF01435
1713:Portal
1655:Lyases
1333:MMP23B
1328:MMP23A
1161:ADAM33
1156:ADAM28
1151:ADAM23
1146:ADAM22
1141:ADAM18
1136:ADAM15
1131:ADAM12
1126:ADAM11
1104:ADAM19
1099:ADAM17
1094:ADAM10
1067:3.4.24
999:(MeSH)
977:MEROPS
957:
947:
906:
896:
847:
837:
803:
793:
785:
746:
736:
728:
702:Nature
578:valine
572:HEXXH
557:cation
508:serine
432:labile
426:, and
424:lysine
396:cobalt
381:ADAM12
371:whose
369:enzyme
340:PDBsum
314:
304:
257:MEROPS
238:CL0126
211:Symbol
182:PDBsum
156:
146:
87:MEROPS
68:CL0126
41:Symbol
1607:Types
1367:Other
1358:MMP28
1353:MMP27
1348:MMP26
1343:MMP25
1338:MMP24
1323:MMP21
1318:MMP20
1313:MMP19
1308:MMP17
1303:MMP16
1298:MMP15
1293:MMP14
1288:MMP13
1283:MMP12
1278:MMP11
1273:MMP10
1121:ADAM8
1116:ADAM7
1111:ADAM2
1089:ADAM9
608:motif
574:motif
532:water
518:as a
510:; T,
377:metal
360:, or
1699:list
1692:EC7
1686:list
1679:EC6
1673:list
1666:EC5
1660:list
1653:EC4
1647:list
1640:EC3
1634:list
1627:EC2
1621:list
1614:EC1
1268:MMP7
1263:MMP3
1256:MMP9
1251:MMP2
1239:MMP8
1234:MMP1
1015:and
1013:Pfam
975:The
955:PMID
931:2010
904:PMID
845:PMID
835:ISBN
801:PMID
783:ISSN
744:PMID
726:ISSN
623:zinc
584:and
490:and
443:EDTA
392:zinc
333:PDBj
329:PDBe
312:ECOD
302:Pfam
286:3b4r
234:clan
232:Pfam
220:Pfam
175:PDBj
171:PDBe
154:ECOD
144:Pfam
116:4aw6
64:clan
62:Pfam
50:Pfam
945:PMC
935:doi
894:PMC
884:doi
827:doi
791:PMC
775:doi
734:PMC
718:doi
706:443
637:of
561:ion
400:ion
320:PDB
274:184
262:M50
162:PDB
128:317
104:394
92:M48
1739::
1064:EC
1058::
1019::
953:.
943:.
929:.
925:.
902:.
892:.
882:.
870:.
866:.
843:.
833:.
813:^
799:.
789:.
781:.
771:22
769:.
765:.
742:.
732:.
724:.
716:.
704:.
700:.
644:.
595:.
549:.
482:,
468:,
453:.
422:,
418:,
414:,
387:.
356:A
331:;
327:;
310:/
173:;
169:;
152:/
1715::
1701:)
1697:(
1688:)
1684:(
1675:)
1671:(
1662:)
1658:(
1649:)
1645:(
1636:)
1632:(
1623:)
1619:(
1443:e
1436:t
1429:v
1069:)
1062:(
1048:e
1041:t
1034:v
961:.
937::
910:.
886::
878::
872:7
851:.
829::
807:.
777::
750:.
720::
712::
472:(
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