EzCatDB: M00168
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DB codeM00168
CATH domainDomain 13.20.20.240 : TIM BarrelCatalytic domain
Domain 23.40.50.280 : Rossmann foldCatalytic domain
Domain 33.20.20.240 : TIM Barrel
Domain 43.40.50.280 : Rossmann fold
Domain 51.10.196.20 : Regulator of G-protein Signalling 4; domain 1
E.C.5.4.99.2
CSA1req
MACiEM0062

CATH domainRelated DB codes (homologues)
3.20.20.240 : TIM BarrelT00236
3.40.50.280 : Rossmann foldM00172,T00236

Enzyme Name
UniProtKBKEGG

P11652P11653
Protein nameMethylmalonyl-CoA mutase small subunitMethylmalonyl-CoA mutase large subunitmethylmalonyl-CoA mutase
methylmalonyl-CoA CoA-carbonyl mutase
methylmalonyl coenzyme A mutase
methylmalonyl coenzyme A carbonylmutase
(S)-methylmalonyl-CoA mutase
(R)-2-methyl-3-oxopropanoyl-CoA CoA-carbonylmutase [incorrect]
SynonymsEC 5.4.99.2
MCB-beta
EC 5.4.99.2
MCM-alpha
PfamPF01642 (MM_CoA_mutase)
[Graphical view]
PF02310 (B12-binding)
PF01642 (MM_CoA_mutase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00280Valine, leucine and isoleucine degradation
MAP00640Propanoate metabolism

UniProtKB:Accession NumberP11652P11653
Entry nameMUTA_PROFRMUTB_PROFR
Activity(R)-methylmalonyl-CoA = succinyl-CoA.(R)-methylmalonyl-CoA = succinyl-CoA.
SubunitHeterodimer of an alpha and a beta chain.Heterodimer of an alpha and a beta chain.
Subcellular location

CofactorAdenosylcobalamin.Adenosylcobalamin.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00194C01213C00091
CompoundCobamide coenzyme(R)-2-Methyl-3-oxopropanoyl-CoASuccinyl-CoA
Typeamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate,heavy metal,nucleoside,nucleotideamine group,carbohydrate,carboxyl group,nucleotide,peptide/protein,sulfide groupamine group,carbohydrate,carboxyl group,nucleotide,peptide/protein,sulfide group
ChEBI
15465
15380
PubChem
449534
439439
92133
439161
           
1e1cA01UnboundAnalogue:DCAUnbound
1e1cC01UnboundAnalogue:DCAUnbound
1reqA01UnboundAnalogue:DCA-GOLUnbound
1reqC01UnboundAnalogue:DCA-GOLUnbound
2reqA01UnboundAnalogue:COAUnbound
2reqC01UnboundAnalogue:COAUnbound
3reqA01Bound:ADNUnboundUnbound
4reqA01Bound:5ADBound:MCABound:SCA
4reqC01Bound:5ADBound:MCABound:SCA
5reqA01UnboundAnalogue:MCDAnalogue:SCD
5reqC01UnboundAnalogue:MCDAnalogue:SCD
6reqA01UnboundUnboundAnalogue:3CP
6reqC01UnboundUnboundAnalogue:3CP
7reqA01UnboundAnalogue:2CPUnbound
7reqC01UnboundAnalogue:2CPUnbound
1e1cA02Analogue:B12UnboundUnbound
1e1cC02Analogue:B12UnboundUnbound
1reqA02Analogue:B12UnboundUnbound
1reqC02Analogue:B12UnboundUnbound
2reqA02Analogue:B12UnboundUnbound
2reqC02Analogue:B12UnboundUnbound
3reqA02Bound:B12UnboundUnbound
4reqA02Bound:B12UnboundUnbound
4reqC02Bound:B12UnboundUnbound
5reqA02Analogue:B12UnboundUnbound
5reqC02Analogue:B12UnboundUnbound
6reqA02Analogue:B12UnboundUnbound
6reqC02Analogue:B12UnboundUnbound
7reqA02Analogue:B12UnboundUnbound
7reqC02Analogue:B12UnboundUnbound
1e1cB01UnboundUnboundUnbound
1e1cD01UnboundUnboundUnbound
1reqB01UnboundUnboundUnbound
1reqD01UnboundUnboundUnbound
2reqB01UnboundUnboundUnbound
2reqD01UnboundUnboundUnbound
3reqB01UnboundUnboundUnbound
4reqB01UnboundUnboundUnbound
4reqD01UnboundUnboundUnbound
5reqB01UnboundUnboundUnbound
5reqD01UnboundUnboundUnbound
6reqB01UnboundUnboundUnbound
6reqD01UnboundUnboundUnbound
7reqB01UnboundUnboundUnbound
7reqD01UnboundUnboundUnbound
1e1cB02UnboundUnboundUnbound
1e1cD02UnboundUnboundUnbound
1reqB02UnboundUnboundUnbound
1reqD02UnboundUnboundUnbound
2reqB02UnboundUnboundUnbound
2reqD02UnboundUnboundUnbound
3reqB02UnboundUnboundUnbound
4reqB02UnboundUnboundUnbound
4reqD02UnboundUnboundUnbound
5reqB02UnboundUnboundUnbound
5reqD02UnboundUnboundUnbound
6reqB02UnboundUnboundUnbound
6reqD02UnboundUnboundUnbound
7reqB02UnboundUnboundUnbound
7reqD02UnboundUnboundUnbound
1e1cB03UnboundUnboundUnbound
1e1cD03UnboundUnboundUnbound
1reqB03UnboundUnboundUnbound
1reqD03UnboundUnboundUnbound
2reqB03UnboundUnboundUnbound
2reqD03UnboundUnboundUnbound
3reqB03UnboundUnboundUnbound
4reqB03UnboundUnboundUnbound
4reqD03UnboundUnboundUnbound
5reqB03UnboundUnboundUnbound
5reqD03UnboundUnboundUnbound
6reqB03UnboundUnboundUnbound
6reqD03UnboundUnboundUnbound
7reqB03UnboundUnboundUnbound
7reqD03UnboundUnboundUnbound

Active-site residues
resource
literature [13], [17], [19]
pdbCatalytic residuesCofactor-binding residuescomment
           
1e1cA01TYR 89;       
 
mutant H244A
1e1cC01TYR 89;       
 
mutant H244A
1reqA01TYR 89;HIS 244
 
 
1reqC01TYR 89;HIS 244
 
 
2reqA01TYR 89;HIS 244
 
 
2reqC01TYR 89;HIS 244
 
 
3reqA01TYR 89;HIS 244
 
 
4reqA01TYR 89;HIS 244
 
 
4reqC01TYR 89;HIS 244
 
 
5reqA01      ;HIS 244
 
mutant Y89F
5reqC01      ;HIS 244
 
mutant Y89F
6reqA01TYR 89;HIS 244
 
 
6reqC01TYR 89;HIS 244
 
 
7reqA01TYR 89;HIS 244
 
 
7reqC01TYR 89;HIS 244
 
 
1e1cA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
1e1cC02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
1reqA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
1reqC02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
2reqA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
2reqC02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
3reqA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
4reqA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
4reqC02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
5reqA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
5reqC02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
6reqA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
6reqC02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
7reqA02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
7reqC02LYS 604;ASP 608
HIS 610(Cobamide coenzyme binding)
 
1e1cB01 
 
 
1e1cD01 
 
 
1reqB01 
 
 
1reqD01 
 
 
2reqB01 
 
 
2reqD01 
 
 
3reqB01 
 
 
4reqB01 
 
 
4reqD01 
 
 
5reqB01 
 
 
5reqD01 
 
 
6reqB01 
 
 
6reqD01 
 
 
7reqB01 
 
 
7reqD01 
 
 
1e1cB02 
 
 
1e1cD02 
 
 
1reqB02 
 
 
1reqD02 
 
 
2reqB02 
 
 
2reqD02 
 
 
3reqB02 
 
 
4reqB02 
 
 
4reqD02 
 
 
5reqB02 
 
 
5reqD02 
 
 
6reqB02 
 
 
6reqD02 
 
 
7reqB02 
 
 
7reqD02 
 
 
1e1cB03 
 
 
1e1cD03 
 
 
1reqB03 
 
 
1reqD03 
 
 
2reqB03 
 
 
2reqD03 
 
 
3reqB03 
 
 
4reqB03 
 
 
4reqD03 
 
 
5reqB03 
 
 
5reqD03 
 
 
6reqB03 
 
 
6reqD03 
 
 
7reqB03 
 
 
7reqD03 
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.11, p.552-553
[2]Scheme 1
[3]Scheme 1
[6]Scheme 1, p.9297-9299
[9]Fig.1, p.345-347
[10]Fig.16, Fig.16, p.299-302
[12]Fig.1, p.293-296
[13]Fig.1, p.14390-14392
[14]p.717-718
[16]Fig.4, p.8002-8004
[17]Scheme II, p.32735-32737
[18]Scheme 1
[19]p.9217-9220
[20]Scheme 1, p.919-922
[22]Fig.1, p.621-624
[23]

[24]Scheme 3, p.2088-2091
[26]Fig.1, Fig.2, p.1075-1078
[27]Fig.1, p.5431
[28]Scheme 1, p.8410-8411
[29]Fig.2, p.8179-8180

references
[1]
PubMed ID2870921
JournalEur J Biochem
Year1986
Volume156
Pages545-54
AuthorsWolfle K, Michenfelder M, Konig A, Hull WE, Retey J
TitleOn the mechanism of action of methylmalonyl-CoA mutase. Change of the steric course on isotope substitution.
[2]
PubMed ID7902085
JournalBiochem J
Year1993
Volume295
Pages387-92
AuthorsKeep NH, Smith GA, Evans MC, Diakun GP, Leadlay PF
TitleThe synthetic substrate succinyl(carbadethia)-CoA generates cob(II)alamin on adenosylcobalamin-dependent methylmalonyl-CoA mutase.
[3]
PubMed ID7957226
JournalEur J Biochem
Year1994
Volume225
Pages891-6
AuthorsZhao Y, Abend A, Kunz M, Such P, Retey J
TitleElectron paramagnetic resonance studies of the methylmalonyl-CoA mutase reaction. Evidence for radical intermediates using natural and artificial substrates as well as the competitive inhibitor 3-carboxypropyl-CoA.
[4]
PubMed ID7578009
JournalBiochemistry
Year1995
Volume34
Pages14125-30
AuthorsCalafat AM, Taoka S, Puckett JM Jr, Semerad C, Yan H, Luo L, Chen H, Banerjee R, Marzilli LG
TitleStructural and electronic similarity but functional difference in methylmalonyl-CoA mutase between coenzyme B12 and the analog 2',5'-dideoxyadenosylcobalamin.
[5]
PubMed ID8722121
JournalBiofactors
Year1995
Volume5
Pages83-6
AuthorsPadmakumar R, Banerjee R
TitleA carbon-skeleton walk: a novel double rearrangement of glutaryl-CoA catalyzed by the human methylmalonyl-CoA mutase.
[6]
PubMed ID7721850
JournalJ Biol Chem
Year1995
Volume270
Pages9295-300
AuthorsPadmakumar R, Banerjee R
TitleEvidence from electron paramagnetic resonance spectroscopy of the participation of radical intermediates in the reaction catalyzed by methylmalonyl-coenzyme A mutase.
[7]
PubMed ID8599754
JournalNat Struct Biol
Year1996
Volume3
Pages316
AuthorsRiddihough G
TitlePicture story. A radical solution.
[8]
PubMed ID8643613
JournalProc Natl Acad Sci U S A
Year1996
Volume93
Pages5550-5
AuthorsDrennan CL, Matthews RG, Rosenblatt DS, Ledley FD, Fenton WA, Ludwig ML
TitleMolecular basis for dysfunction of some mutant forms of methylmalonyl-CoA mutase: deductions from the structure of methionine synthase.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID96398619
PubMed ID8805541
JournalStructure
Year1996
Volume4
Pages339-50
AuthorsMancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bosecke P, Diat O, Evans PR
TitleHow coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution.
Related PDB1req
Related UniProtKBP11652,P11653
[10]
PubMed ID9242908
JournalAnnu Rev Biochem
Year1997
Volume66
Pages269-313
AuthorsLudwig ML, Matthews RG
TitleStructure-based perspectives on B12-dependent enzymes.
[11]
PubMed ID9363770
JournalEur J Biochem
Year1997
Volume249
Pages180-6
AuthorsAbend A, Illich V, Retey J
TitleFurther insights into the mechanism of action of methylmalonyl-CoA mutase by electron paramagnetic resonance studies.
[12]
PubMed ID9765867
JournalBiochem Soc Trans
Year1998
Volume26
Pages293-8
AuthorsThoma NH, Leadlay PF
TitleMechanistic and structural studies on methylmalonyl-CoA mutase.
[13]
CommentsX-ray crystallography
PubMed ID9772164
JournalBiochemistry
Year1998
Volume37
Pages14386-93
AuthorsThoma NH, Meier TW, Evans PR, Leadlay PF
TitleStabilization of radical intermediates by an active-site tyrosine residue in methylmalonyl-CoA mutase.
Related PDB5req
[14]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID98322359
PubMed ID9655823
JournalStructure
Year1998
Volume6
Pages711-20
AuthorsMancia F, Evans PR
TitleConformational changes on substrate binding to methylmalonyl CoA mutase and new insights into the free radical mechanism.
Related PDB2req,3req
Related UniProtKBP11652,P11653
[15]
PubMed ID10563814
JournalBiochemistry
Year1999
Volume38
Pages15287-94
AuthorsChowdhury S, Banerjee R
TitleRole of the dimethylbenzimidazole tail in the reaction catalyzed by coenzyme B12-dependent methylmalonyl-CoA mutase.
[16]
CommentsX-ray crystallography
PubMed ID10387043
JournalBiochemistry
Year1999
Volume38
Pages7999-8005
AuthorsMancia F, Smith GA, Evans PR
TitleCrystal structure of substrate complexes of methylmalonyl-CoA mutase.
Related PDB4req,6req,7req
[17]
PubMed ID10551831
JournalJ Biol Chem
Year1999
Volume274
Pages32733-7
AuthorsMaiti N, Widjaja L, Banerjee R
TitleProton transfer from histidine 244 may facilitate the 1,2 rearrangement reaction in coenzyme B(12)-dependent methylmalonyl-CoA mutase.
[18]
PubMed ID10891081
JournalBiochemistry
Year2000
Volume39
Pages7998-8006
AuthorsChowdhury S, Banerjee R
TitleThermodynamic and kinetic characterization of Co-C bond homolysis catalyzed by coenzyme B(12)-dependent methylmalonyl-CoA mutase.
[19]
CommentsX-ray crystallography
PubMed ID10924114
JournalBiochemistry
Year2000
Volume39
Pages9213-21
AuthorsThoma NH, Evans PR, Leadlay PF
TitleProtection of radical intermediates at the active site of adenosylcobalamin-dependent methylmalonyl-CoA mutase.
Related PDB1e1c
[20]
PubMed ID11948881
JournalChembiochem
Year2001
Volume2
Pages919-22
AuthorsWetmore SD, Smith DM, Radom L
TitleCatalysis by mutants of methylmalonyl-CoA mutase: a theoretical rationalization for a change in the rate-determining step.
[21]
PubMed ID11031263
JournalJ Biol Chem
Year2001
Volume276
Pages1015-9
AuthorsChowdhury S, Thomas MG, Escalante-Semerena JC, Banerjee R
TitleThe coenzyme b12 analog 5'-deoxyadenosylcobinamide-gdp supports catalysis by methylmalonyl-coa mutase in the absence of trans-ligand coordination.
[22]
PubMed ID12196149
JournalBiochem Soc Trans
Year2002
Volume30
Pages621-4
AuthorsBanerjee R, Vlasie M
TitleControlling the reactivity of radical intermediates by coenzyme B(12)-dependent methylmalonyl-CoA mutase.
[23]
PubMed ID11893736
JournalJ Biol Chem
Year2002
Volume277
Pages18523-7
AuthorsVlasie M, Chowdhury S, Banerjee R
TitleImportance of the histidine ligand to coenzyme B12 in the reaction catalyzed by methylmalonyl-CoA mutase.
[24]
PubMed ID12797824
JournalChem Rev
Year2003
Volume103
Pages2083-94
AuthorsBanerjee R
TitleRadical carbon skeleton rearrangements: catalysis by coenzyme B12-dependent mutases.
[25]
PubMed ID12569457
JournalChemistry
Year2003
Volume9
Pages652-60
AuthorsWeigl U, Heimberger M, Pierik AJ, Retey J
TitleSynthesis of enantiomerically-pure [13C]aristeromycylcobalamin and its reactivity in dioldehydratase, glyceroldehydratase, ethanolamine ammonia-lyase and methylmalonyl-CoA mutase reactions.
[26]
PubMed ID12537507
JournalJ Am Chem Soc
Year2003
Volume125
Pages1072-8
AuthorsLoferer MJ, Webb BM, Grant GH, Liedl KR
TitleEnergetic and stereochemical effects of the protein environment on substrate: a theoretical study of methylmalonyl-CoA mutase.
[27]
PubMed ID12720457
JournalJ Am Chem Soc
Year2003
Volume125
Pages5431-5
AuthorsVlasie MD, Banerjee R
TitleTyrosine 89 accelerates Co-carbon bond homolysis in methylmalonyl-CoA mutase.
[28]
PubMed ID15222752
JournalBiochemistry
Year2004
Volume43
Pages8410-7
AuthorsVlasie MD, Banerjee R
TitleWhen a spectator turns killer: suicidal electron transfer from cobalamin in methylmalonyl-CoA mutase.
[29]
PubMed ID15225058
JournalJ Am Chem Soc
Year2004
Volume126
Pages8167-80
AuthorsBrooks AJ, Vlasie M, Banerjee R, Brunold TC
TitleSpectroscopic and computational studies on the adenosylcobalamin-dependent methylmalonyl-CoA mutase: evaluation of enzymatic contributions to Co-C bond activation in the Co3+ ground state.
[30]
PubMed ID15113202
JournalJ Am Chem Soc
Year2004
Volume126
Pages5368-9
AuthorsDaublain P, Horner JH, Kuznetsov A, Newcomb M
TitleSolvent polarity effects and limited acid catalysis in rearrangements of model radicals for the methylmalonyl-CoA mutase- and isobutyryl-CoA mutase-catalyzed isomerization reactions.

comments
This enzyme catalyzes radical reactions.

createdupdated
2005-05-272009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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