Protein Domain : IPR011822

Type:  Family Name:  Cobalamin-dependent methionine synthase
Description:  Cobalamin (vitamin B12) dependent methionine synthase (MetH; 5-methyltetrahydrofolate--homocysteine S-methyltransferase) catalyses the conversion of 5-methyltetrahydrofolate and L-homocysteine to tetrahydrofolate and L-methionine as the final step in de novomethionine biosynthesis. The enzyme requires methylcobalamin as a cofactor. In humans, defects in this enzyme are the cause of autosomal recessive inherited methylcobalamin deficiency (CBLG), which causes mental retardation, macrocytic anemia and homocystinuria. Mild deficiencies in activity may result in mild hyperhomocysteinemia, and mutations in the enzyme may be involved in tumorigenesis. Vitamin B12 dependent methionine synthase is found in prokaryotes and eukaryotes, but in prokaryotes the cofactor is cobalamin.This enzyme is a large protein composed of four structurally and functionally distinct modules: the first two modules bind homocysteine and tetrahydrofolate [], the third module binds the B12 cofactor [], and the C-terminal module (activation domain) binds S-adenosylmethionine. The activation domain is essential for the reductive activation of the enzyme. During the catalytic cycle, the highly reactive cob(I)alamin intermediate can be oxidised to produce an inactive cob(II)alamin enzyme; the enzyme is then reactivated via reductive methylation by the activation domain []. The activation domain adopts an unusual alpha/beta fold.Recent studies suggest that this enzyme exists as an ensemble of conformations with equilibria dependent on the oxidation and methylation state of the cobalamin and on the concentrations of substrates or products []. Short Name:  MetH
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0 Child Features

6 Contains

DB identifier Type Name
IPR006158 Domain Cobalamin (vitamin B12)-binding domain
IPR003726 Domain Homocysteine-binding domain
IPR000489 Domain Pterin-binding domain
IPR011005 Domain Dihydropteroate synthase-like
IPR003759 Domain Cobalamin (vitamin B12)-binding module, cap domain
IPR004223 Domain Vitamin B12-dependent methionine synthase, activation domain

2 Cross Referencess

Identifier
PIRSF000381
TIGR02082

0 Found In

5 GO Annotations

GO Term Gene Name
GO:0008270 IPR011822
GO:0008705 IPR011822
GO:0008898 IPR011822
GO:0031419 IPR011822
GO:0009086 IPR011822

5 Ontology Annotations

GO Term Gene Name
GO:0008270 IPR011822
GO:0008705 IPR011822
GO:0008898 IPR011822
GO:0031419 IPR011822
GO:0009086 IPR011822

0 Parent Features

14 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
148156 PAC:27345998 Micromonas pusilla CCMP1545 1335  
105867 C1EAX2 PAC:27404440 Micromonas sp RCC299 1378  
45056 A4RUZ2 PAC:27413128 Ostreococcus lucimarinus 1252  
Dusal.0126s00011.2.p PAC:33196528 Dunaliella salina 2677  
Brdisv1pangenome1007940m.p PAC:33619161 Brachypodium distachyon Pangenome 1292  
Brdisv1pangenome1009339m.p PAC:33657227 Brachypodium distachyon Pangenome 1211  
Brdisv1BdTR11A1045202m.p PAC:35691909 Brachypodium distachyon BdTR11a 1103  
Brdisv1BdTR11A1042019m.p PAC:35693972 Brachypodium distachyon BdTR11a 1236  
Brdisv1BdTR11A1040584m.p PAC:35692838 Brachypodium distachyon BdTR11a 1211  
Brdisv1BdTR11A1040255m.p PAC:35690222 Brachypodium distachyon BdTR11a 1292  
Pum0927s0005.1.p A0A1X6NND8 PAC:38014178 Porphyra umbilicalis 1262  
Cz15g06080.t1 PAC:38234509 Chromochloris zofingiensis 787  
Bobra.0035s0068.1.p PAC:40717602 Botryococcus braunii 2805  
Vocar.0006s0021.1.p PAC:32894136 Volvox carteri 2811  

4 Publications

First Author Title Year Journal Volume Pages PubMed ID
            14752199
            11731805
            7992050
            12832615