424:
1238:
512:
228:
458:
as well as its associated iron-containing co-factor. Several species of methanogens have been characterized that express enzymes in the Hmd hydrogenase family. Between species the enzyme is found with differing numbers of sub-units and some minor amino acid sequence variations. The monomer is
517:
Although the mechanism by which Hmd acts is unknown, the iron-containing cofactor is in part responsible for the catalytic activity. High concentrations of CO inhibit the enzyme as well, implicating iron as the center of catalysis. It has been proposed that the iron functions to bind
646:
Shima S, Lyon EJ, Sordel-Klippert M, Kauss M, Kahnt J, Thauer RK, Steinbach K, Xie X, Verdier L, Griesinger C (May 2004). "The cofactor of the iron-sulfur cluster free hydrogenase hmd: structure of the light-inactivation product".
423:
492:
without the co-factor results in an inactive holoenzyme. However, hydrogenase activity can be rescued by the addition of the iron-containing co-factor taken from denatured active enzyme.
775:
182:
307:
507:. On the basis of spectroscopic characterization, Shima et al. have proposed a structure for this organic cofactor (minus the iron atom and CO molecules) as shown:
407:. The natural substrate of the enzyme is the organic compound methenyltetrahydromethanopterin. The organic compound includes a methenyl group bound to two tertiary
466:
causes the release of an iron atom and two molecules of carbon monoxide. In the holoenzyme the Fe and CO molecules are found associated with a 542 Da cofactor.
201:
495:
As mentioned, irradiation of the co-factor with UV light results in the loss of CO and Fe. In addition the 542 Da compound can be further degraded by a
396:. One step in methanogenesis entails conversion of a methenyl group (formic acid oxidation state) to a methylene group (formaldehyde oxidation state).
768:
901:
1263:
419:
to methylenetetrahydromethanopterin as shown. Eventually the methylene group is further reduced and released as a molecule of methane.
957:
761:
441:
is always added to the pro-R face. In the reverse reaction stereospecificity is maintained and the highlighted hydride is removed.
194:
364:
855:
819:
814:
145:
121:
1113:
327:
1228:
475:
1098:
1214:
1201:
1188:
1175:
1162:
1149:
1136:
916:
891:
883:
865:
847:
837:
829:
801:
139:
1108:
1062:
1005:
792:
32:
315:
126:
1010:
483:
924:
873:
809:
206:
753:
511:
114:
1031:
950:
1103:
311:
49:
522:
and the substrate methenyltetrahydromethanopterin, organizing these two reactants in close proximity.
733:
369:
584:
579:
577:
474:
The iron-containing co-factor is found tightly associated with the protein. It can be released upon
142:
1258:
1067:
66:
44:
1000:
712:
602:
Lyon EJ, Shima S, Buurman G, Chowdhuri S, Batschauer A, Steinbach K, Thauer RK (January 2004).
704:
664:
625:
604:"UV-A/blue-light inactivation of the 'metal-free' hydrogenase (Hmd) from methanogenic archaea"
563:
499:(which specifically cleaves phosphate bonds). Hydrolysis of the phosphate bonds generates the
496:
479:
463:
302:
133:
399:
Among the hydrogenase family of enzymes, Hmd is unique in that it does not directly reduce CO
1046:
1041:
1015:
943:
741:
696:
656:
615:
555:
488:
102:
294:
1093:
1077:
990:
906:
78:
37:
737:
232:
the crystal structure of the apoenzyme of the iron-sulfur-cluster-free hydrogenase (hmd)
1242:
1131:
1072:
784:
500:
434:
177:
157:
1252:
1036:
995:
620:
603:
459:
approximately 45,000 Da in mass, although this value varies from species to species.
152:
745:
716:
256:
985:
546:
Shima S, Thauer RK (2007). "A third type of hydrogenase catalyzing H2 activation".
356:
290:
415:
before being incorporated into the substrate, which is catalytically reduced by H
268:
1209:
1144:
980:
373:
161:
1237:
504:
462:
The enzymatic activity of the enzyme is lost upon exposure to sunlight or UV.
1183:
1157:
724:
Karyakin AA, Varfolomeev SD (1986). "Catalytic
Properties of Hydrogenases".
455:
668:
660:
629:
567:
708:
227:
788:
385:
263:
90:
376:
are enzymes that either reduce protons or oxidize molecular dihydrogen.
700:
430:
393:
368:. It was discovered and first characterized by the Thauer group at the
109:
559:
1196:
966:
359:
352:
322:
189:
85:
73:
61:
437:. Given that the substrate is planar the hydride originating from H
1170:
408:
585:"EC 1.12.98.2 - 5,10-methenyltetrahydromethanopterin hydrogenase"
221:
H2-forming N5,N10-methylene-tetrahydromethanopterin dehydrogenase
284:
251:
97:
939:
757:
935:
1226:
589:
1122:
1086:
1055:
1024:
973:
915:
882:
864:
846:
828:
800:
321:
301:
283:
278:
262:
250:
242:
237:
220:
200:
188:
176:
171:
151:
132:
120:
108:
96:
84:
72:
60:
55:
43:
31:
26:
21:
897:5,10-Methenyltetrahydromethanopterin hydrogenase
341:5,10-methenyltetrahydromethanopterin hydrogenase
22:5,10-methenyltetrahydromethanopterin hydrogenase
641:
639:
541:
539:
537:
535:
951:
769:
687:Blaut M (1994). "Metabolism of methanogens".
8:
958:
944:
936:
776:
762:
754:
275:
226:
168:
619:
454:The Hmd holoenzyme includes the protein
1233:
531:
503:guanosine monophosphate and a modified
591:. Technische Universität Braunschweig.
217:
18:
411:. The methenyl group originated as CO
7:
902:Methanosarcina-phenazine hydrogenase
384:Methanogens rely on such enzymes to
349:iron-sulfur cluster-free hydrogenase
433:transfer has also been shown to be
14:
1236:
621:10.1046/j.1432-1033.2003.03920.x
510:
486:. Expression of the Hmd gene in
445:Chemical and physical properties
422:
365:Methanothermobacter marburgensis
856:Hydrogen:quinone oxidoreductase
746:10.1070/rc1986v055n09abeh003228
820:Hydrogenase (NAD+, ferredoxin)
815:Hydrogen dehydrogenase (NADP+)
1:
279:Available protein structures:
470:Hmd iron-containing cofactor
1280:
1264:Enzymes of known structure
649:Angew. Chem. Int. Ed. Engl
1114:Michaelis–Menten kinetics
892:Coenzyme F420 hydrogenase
838:Cytochrome-c3 hydrogenase
274:
225:
167:
1006:Diffusion-limited enzyme
726:Russian Chemical Reviews
689:Antonie van Leeuwenhoek
484:guanidine hydrochloride
925:Hydrogenase (acceptor)
874:Ferredoxin hydrogenase
810:Hydrogen dehydrogenase
661:10.1002/anie.200353763
1099:Eadie–Hofstee diagram
1032:Allosteric regulation
1109:Lineweaver–Burk plot
370:Max Planck Institute
738:1986RuCRv..55..867K
548:The Chemical Record
388:the reduction of CO
1068:Enzyme superfamily
1001:Enzyme promiscuity
701:10.1007/BF00871639
1224:
1223:
933:
932:
560:10.1002/tcr.20111
497:phosphodiesterase
480:2-mercaptoethanol
347:), the so-called
337:
336:
333:
332:
328:structure summary
216:
215:
212:
211:
115:metabolic pathway
1271:
1241:
1240:
1232:
1104:Hanes–Woolf plot
1047:Enzyme activator
1042:Enzyme inhibitor
1016:Enzyme catalysis
960:
953:
946:
937:
778:
771:
764:
755:
749:
720:
695:(1–3): 187–208.
673:
672:
643:
634:
633:
623:
599:
593:
592:
581:
572:
571:
543:
514:
426:
276:
230:
218:
169:
19:
16:Class of enzymes
1279:
1278:
1274:
1273:
1272:
1270:
1269:
1268:
1249:
1248:
1247:
1235:
1227:
1225:
1220:
1132:Oxidoreductases
1118:
1094:Enzyme kinetics
1082:
1078:List of enzymes
1051:
1020:
991:Catalytic triad
969:
964:
934:
929:
911:
907:Sulfhydrogenase
878:
860:
842:
824:
796:
785:Oxidoreductases
782:
752:
723:
686:
682:
680:Further reading
677:
676:
655:(19): 2547–51.
645:
644:
637:
608:Eur. J. Biochem
601:
600:
596:
583:
582:
575:
545:
544:
533:
528:
521:
472:
452:
447:
440:
418:
414:
406:
402:
391:
382:
380:Enzyme function
233:
17:
12:
11:
5:
1277:
1275:
1267:
1266:
1261:
1251:
1250:
1246:
1245:
1222:
1221:
1219:
1218:
1205:
1192:
1179:
1166:
1153:
1140:
1126:
1124:
1120:
1119:
1117:
1116:
1111:
1106:
1101:
1096:
1090:
1088:
1084:
1083:
1081:
1080:
1075:
1070:
1065:
1059:
1057:
1056:Classification
1053:
1052:
1050:
1049:
1044:
1039:
1034:
1028:
1026:
1022:
1021:
1019:
1018:
1013:
1008:
1003:
998:
993:
988:
983:
977:
975:
971:
970:
965:
963:
962:
955:
948:
940:
931:
930:
928:
927:
921:
919:
913:
912:
910:
909:
904:
899:
894:
888:
886:
880:
879:
877:
876:
870:
868:
862:
861:
859:
858:
852:
850:
844:
843:
841:
840:
834:
832:
826:
825:
823:
822:
817:
812:
806:
804:
798:
797:
783:
781:
780:
773:
766:
758:
751:
750:
732:(9): 867–882.
721:
683:
681:
678:
675:
674:
635:
614:(1): 195–204.
594:
573:
530:
529:
527:
524:
519:
501:ribonucleotide
471:
468:
451:
450:Hmd holoenzyme
448:
446:
443:
438:
435:stereospecific
416:
412:
404:
400:
389:
381:
378:
335:
334:
331:
330:
325:
319:
318:
305:
299:
298:
288:
281:
280:
272:
271:
266:
260:
259:
254:
248:
247:
244:
240:
239:
235:
234:
231:
223:
222:
214:
213:
210:
209:
204:
198:
197:
192:
186:
185:
180:
174:
173:
165:
164:
155:
149:
148:
137:
130:
129:
124:
118:
117:
112:
106:
105:
100:
94:
93:
88:
82:
81:
76:
70:
69:
64:
58:
57:
53:
52:
47:
41:
40:
35:
29:
28:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1276:
1265:
1262:
1260:
1257:
1256:
1254:
1244:
1239:
1234:
1230:
1216:
1212:
1211:
1206:
1203:
1199:
1198:
1193:
1190:
1186:
1185:
1180:
1177:
1173:
1172:
1167:
1164:
1160:
1159:
1154:
1151:
1147:
1146:
1141:
1138:
1134:
1133:
1128:
1127:
1125:
1121:
1115:
1112:
1110:
1107:
1105:
1102:
1100:
1097:
1095:
1092:
1091:
1089:
1085:
1079:
1076:
1074:
1073:Enzyme family
1071:
1069:
1066:
1064:
1061:
1060:
1058:
1054:
1048:
1045:
1043:
1040:
1038:
1037:Cooperativity
1035:
1033:
1030:
1029:
1027:
1023:
1017:
1014:
1012:
1009:
1007:
1004:
1002:
999:
997:
996:Oxyanion hole
994:
992:
989:
987:
984:
982:
979:
978:
976:
972:
968:
961:
956:
954:
949:
947:
942:
941:
938:
926:
923:
922:
920:
918:
914:
908:
905:
903:
900:
898:
895:
893:
890:
889:
887:
885:
881:
875:
872:
871:
869:
867:
863:
857:
854:
853:
851:
849:
845:
839:
836:
835:
833:
831:
827:
821:
818:
816:
813:
811:
808:
807:
805:
803:
799:
794:
790:
786:
779:
774:
772:
767:
765:
760:
759:
756:
747:
743:
739:
735:
731:
727:
722:
718:
714:
710:
706:
702:
698:
694:
690:
685:
684:
679:
670:
666:
662:
658:
654:
650:
642:
640:
636:
631:
627:
622:
617:
613:
609:
605:
598:
595:
590:
586:
580:
578:
574:
569:
565:
561:
557:
553:
549:
542:
540:
538:
536:
532:
525:
523:
515:
513:
508:
506:
502:
498:
493:
491:
490:
485:
481:
477:
469:
467:
465:
460:
457:
449:
444:
442:
436:
432:
427:
425:
420:
410:
397:
395:
387:
379:
377:
375:
371:
367:
366:
361:
358:
354:
350:
346:
342:
329:
326:
324:
320:
317:
313:
309:
306:
304:
300:
296:
292:
289:
286:
282:
277:
273:
270:
267:
265:
261:
258:
255:
253:
249:
245:
241:
236:
229:
224:
219:
208:
205:
203:
199:
196:
193:
191:
187:
184:
181:
179:
175:
170:
166:
163:
159:
156:
154:
153:Gene Ontology
150:
147:
144:
141:
138:
135:
131:
128:
125:
123:
119:
116:
113:
111:
107:
104:
101:
99:
95:
92:
91:NiceZyme view
89:
87:
83:
80:
77:
75:
71:
68:
65:
63:
59:
54:
51:
48:
46:
42:
39:
36:
34:
30:
25:
20:
1210:Translocases
1207:
1194:
1181:
1168:
1155:
1145:Transferases
1142:
1129:
986:Binding site
896:
787:: Acting on
729:
725:
692:
688:
652:
648:
611:
607:
597:
588:
554:(1): 37–46.
551:
547:
516:
509:
494:
487:
476:denaturation
473:
461:
453:
428:
421:
398:
383:
374:Hydrogenases
372:in Marburg.
363:
357:methanogenic
348:
344:
340:
338:
79:BRENDA entry
50:100357-01-5
981:Active site
238:Identifiers
67:IntEnz view
27:Identifiers
1259:EC 1.12.98
1253:Categories
1184:Isomerases
1158:Hydrolases
1025:Regulation
791:as donor (
526:References
505:2-pyridone
464:Photolysis
291:structures
136:structures
103:KEGG entry
1063:EC number
456:homodimer
355:found in
269:IPR004889
56:Databases
38:1.12.98.2
1087:Kinetics
1011:Cofactor
974:Activity
789:hydrogen
717:23706408
669:15127449
630:14686932
568:17304591
386:catalyze
362:such as
351:, is an
308:RCSB PDB
264:InterPro
207:proteins
195:articles
183:articles
140:RCSB PDB
1243:Biology
1197:Ligases
967:Enzymes
917:1.10.99
884:1.10.98
734:Bibcode
709:7747931
489:E. coli
431:hydride
394:methane
257:PF03201
162:QuickGO
127:profile
110:MetaCyc
45:CAS no.
1229:Portal
1171:Lyases
866:1.12.7
848:1.12.5
830:1.12.2
802:1.12.1
715:
707:
667:
628:
566:
409:amides
360:archea
353:enzyme
323:PDBsum
297:
287:
243:Symbol
190:PubMed
172:Search
158:AmiGO
146:PDBsum
86:ExPASy
74:BRENDA
62:IntEnz
33:EC no.
1123:Types
795:1.12)
713:S2CID
478:with
403:to CH
122:PRIAM
1215:list
1208:EC7
1202:list
1195:EC6
1189:list
1182:EC5
1176:list
1169:EC4
1163:list
1156:EC3
1150:list
1143:EC2
1137:list
1130:EC1
705:PMID
665:PMID
626:PMID
564:PMID
429:The
343:(or
339:The
316:PDBj
312:PDBe
295:ECOD
285:Pfam
252:Pfam
202:NCBI
143:PDBe
98:KEGG
742:doi
697:doi
657:doi
616:doi
612:271
556:doi
482:or
392:to
345:Hmd
303:PDB
246:HMD
178:PMC
134:PDB
1255::
793:EC
740:.
730:55
728:.
711:.
703:.
693:66
691:.
663:.
653:43
651:.
638:^
624:.
610:.
606:.
587:.
576:^
562:.
550:.
534:^
314:;
310:;
293:/
160:/
1231::
1217:)
1213:(
1204:)
1200:(
1191:)
1187:(
1178:)
1174:(
1165:)
1161:(
1152:)
1148:(
1139:)
1135:(
959:e
952:t
945:v
777:e
770:t
763:v
748:.
744::
736::
719:.
699::
671:.
659::
632:.
618::
570:.
558::
552:7
520:2
518:H
439:2
417:2
413:2
405:4
401:2
390:2
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