DB code: M00168

CATH domain 3.20.20.240 : TIM Barrel Catalytic domain
3.40.50.280 : Rossmann fold Catalytic domain
3.20.20.240 : TIM Barrel
3.40.50.280 : Rossmann fold
1.10.196.20 : Regulator of G-protein Signalling 4; domain 1
E.C. 5.4.99.2
CSA 1req
M-CSA 1req
MACiE M0062

CATH domain Related DB codes (homologues)
3.20.20.240 : TIM Barrel T00236
3.40.50.280 : Rossmann fold M00172 T00236

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P11652 Methylmalonyl-CoA mutase small subunit
EC 5.4.99.2
MCB-beta
PF01642 (MM_CoA_mutase)
[Graphical View]
P11653 Methylmalonyl-CoA mutase large subunit
EC 5.4.99.2
MCM-alpha
PF02310 (B12-binding)
PF01642 (MM_CoA_mutase)
[Graphical View]

KEGG enzyme name
methylmalonyl-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]

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P11652 MUTA_PROFR (R)-methylmalonyl-CoA = succinyl-CoA. Heterodimer of an alpha and a beta chain. Adenosylcobalamin.
P11653 MUTB_PROFR (R)-methylmalonyl-CoA = succinyl-CoA. Heterodimer of an alpha and a beta chain. Adenosylcobalamin.

KEGG Pathways
Map code Pathways E.C.
MAP00280 Valine, leucine and isoleucine degradation
MAP00640 Propanoate metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00194 C01213 C00091
E.C.
Compound Cobamide coenzyme (R)-2-Methyl-3-oxopropanoyl-CoA Succinyl-CoA
Type amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate,heavy metal,nucleoside,nucleotide amine group,carbohydrate,carboxyl group,nucleotide ,peptide/protein,sulfide group amine group,carbohydrate,carboxyl group,nucleotide ,peptide/protein,sulfide group
ChEBI 15465
15465
15380
15380
PubChem 439439
449534
439439
449534
439161
92133
439161
92133
1e1cA01 Unbound Analogue:DCA Unbound
1e1cC01 Unbound Analogue:DCA Unbound
1reqA01 Unbound Analogue:DCA-GOL Unbound
1reqC01 Unbound Analogue:DCA-GOL Unbound
2reqA01 Unbound Analogue:COA Unbound
2reqC01 Unbound Analogue:COA Unbound
3reqA01 Bound:ADN Unbound Unbound
4reqA01 Bound:5AD Bound:MCA Bound:SCA
4reqC01 Bound:5AD Bound:MCA Bound:SCA
5reqA01 Unbound Analogue:MCD Analogue:SCD
5reqC01 Unbound Analogue:MCD Analogue:SCD
6reqA01 Unbound Unbound Analogue:3CP
6reqC01 Unbound Unbound Analogue:3CP
7reqA01 Unbound Analogue:2CP Unbound
7reqC01 Unbound Analogue:2CP Unbound
1e1cA02 Analogue:B12 Unbound Unbound
1e1cC02 Analogue:B12 Unbound Unbound
1reqA02 Analogue:B12 Unbound Unbound
1reqC02 Analogue:B12 Unbound Unbound
2reqA02 Analogue:B12 Unbound Unbound
2reqC02 Analogue:B12 Unbound Unbound
3reqA02 Bound:B12 Unbound Unbound
4reqA02 Bound:B12 Unbound Unbound
4reqC02 Bound:B12 Unbound Unbound
5reqA02 Analogue:B12 Unbound Unbound
5reqC02 Analogue:B12 Unbound Unbound
6reqA02 Analogue:B12 Unbound Unbound
6reqC02 Analogue:B12 Unbound Unbound
7reqA02 Analogue:B12 Unbound Unbound
7reqC02 Analogue:B12 Unbound Unbound
1e1cB01 Unbound Unbound Unbound
1e1cD01 Unbound Unbound Unbound
1reqB01 Unbound Unbound Unbound
1reqD01 Unbound Unbound Unbound
2reqB01 Unbound Unbound Unbound
2reqD01 Unbound Unbound Unbound
3reqB01 Unbound Unbound Unbound
4reqB01 Unbound Unbound Unbound
4reqD01 Unbound Unbound Unbound
5reqB01 Unbound Unbound Unbound
5reqD01 Unbound Unbound Unbound
6reqB01 Unbound Unbound Unbound
6reqD01 Unbound Unbound Unbound
7reqB01 Unbound Unbound Unbound
7reqD01 Unbound Unbound Unbound
1e1cB02 Unbound Unbound Unbound
1e1cD02 Unbound Unbound Unbound
1reqB02 Unbound Unbound Unbound
1reqD02 Unbound Unbound Unbound
2reqB02 Unbound Unbound Unbound
2reqD02 Unbound Unbound Unbound
3reqB02 Unbound Unbound Unbound
4reqB02 Unbound Unbound Unbound
4reqD02 Unbound Unbound Unbound
5reqB02 Unbound Unbound Unbound
5reqD02 Unbound Unbound Unbound
6reqB02 Unbound Unbound Unbound
6reqD02 Unbound Unbound Unbound
7reqB02 Unbound Unbound Unbound
7reqD02 Unbound Unbound Unbound
1e1cB03 Unbound Unbound Unbound
1e1cD03 Unbound Unbound Unbound
1reqB03 Unbound Unbound Unbound
1reqD03 Unbound Unbound Unbound
2reqB03 Unbound Unbound Unbound
2reqD03 Unbound Unbound Unbound
3reqB03 Unbound Unbound Unbound
4reqB03 Unbound Unbound Unbound
4reqD03 Unbound Unbound Unbound
5reqB03 Unbound Unbound Unbound
5reqD03 Unbound Unbound Unbound
6reqB03 Unbound Unbound Unbound
6reqD03 Unbound Unbound Unbound
7reqB03 Unbound Unbound Unbound
7reqD03 Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [13], [17], [19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1e1cA01 TYR 89; mutant H244A
1e1cC01 TYR 89; mutant H244A
1reqA01 TYR 89;HIS 244
1reqC01 TYR 89;HIS 244
2reqA01 TYR 89;HIS 244
2reqC01 TYR 89;HIS 244
3reqA01 TYR 89;HIS 244
4reqA01 TYR 89;HIS 244
4reqC01 TYR 89;HIS 244
5reqA01 ;HIS 244 mutant Y89F
5reqC01 ;HIS 244 mutant Y89F
6reqA01 TYR 89;HIS 244
6reqC01 TYR 89;HIS 244
7reqA01 TYR 89;HIS 244
7reqC01 TYR 89;HIS 244
1e1cA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
1e1cC02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
1reqA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
1reqC02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
2reqA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
2reqC02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
3reqA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
4reqA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
4reqC02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
5reqA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
5reqC02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
6reqA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
6reqC02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
7reqA02 LYS 604;ASP 608 HIS 610(Cobamide coenzyme binding)
7reqC02 LYS 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
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 2870921
Journal Eur J Biochem
Year 1986
Volume 156
Pages 545-54
Authors Wolfle K, Michenfelder M, Konig A, Hull WE, Retey J
Title On the mechanism of action of methylmalonyl-CoA mutase. Change of the steric course on isotope substitution.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7902085
Journal Biochem J
Year 1993
Volume 295
Pages 387-92
Authors Keep NH, Smith GA, Evans MC, Diakun GP, Leadlay PF
Title The synthetic substrate succinyl(carbadethia)-CoA generates cob(II)alamin on adenosylcobalamin-dependent methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7957226
Journal Eur J Biochem
Year 1994
Volume 225
Pages 891-6
Authors Zhao Y, Abend A, Kunz M, Such P, Retey J
Title Electron 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.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7578009
Journal Biochemistry
Year 1995
Volume 34
Pages 14125-30
Authors Calafat AM, Taoka S, Puckett JM Jr, Semerad C, Yan H, Luo L, Chen H, Banerjee R, Marzilli LG
Title Structural and electronic similarity but functional difference in methylmalonyl-CoA mutase between coenzyme B12 and the analog 2',5'-dideoxyadenosylcobalamin.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8722121
Journal Biofactors
Year 1995
Volume 5
Pages 83-6
Authors Padmakumar R, Banerjee R
Title A carbon-skeleton walk: a novel double rearrangement of glutaryl-CoA catalyzed by the human methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7721850
Journal J Biol Chem
Year 1995
Volume 270
Pages 9295-300
Authors Padmakumar R, Banerjee R
Title Evidence from electron paramagnetic resonance spectroscopy of the participation of radical intermediates in the reaction catalyzed by methylmalonyl-coenzyme A mutase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8599754
Journal Nat Struct Biol
Year 1996
Volume 3
Pages 316
Authors Riddihough G
Title Picture story. A radical solution.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8643613
Journal Proc Natl Acad Sci U S A
Year 1996
Volume 93
Pages 5550-5
Authors Drennan CL, Matthews RG, Rosenblatt DS, Ledley FD, Fenton WA, Ludwig ML
Title Molecular basis for dysfunction of some mutant forms of methylmalonyl-CoA mutase: deductions from the structure of methionine synthase.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 96398619
PubMed ID 8805541
Journal Structure
Year 1996
Volume 4
Pages 339-50
Authors Mancia F, Keep NH, Nakagawa A, Leadlay PF, McSweeney S, Rasmussen B, Bosecke P, Diat O, Evans PR
Title How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution.
Related PDB 1req
Related UniProtKB P11652 P11653
[10]
Resource
Comments
Medline ID
PubMed ID 9242908
Journal Annu Rev Biochem
Year 1997
Volume 66
Pages 269-313
Authors Ludwig ML, Matthews RG
Title Structure-based perspectives on B12-dependent enzymes.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 9363770
Journal Eur J Biochem
Year 1997
Volume 249
Pages 180-6
Authors Abend A, Illich V, Retey J
Title Further insights into the mechanism of action of methylmalonyl-CoA mutase by electron paramagnetic resonance studies.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9765867
Journal Biochem Soc Trans
Year 1998
Volume 26
Pages 293-8
Authors Thoma NH, Leadlay PF
Title Mechanistic and structural studies on methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9772164
Journal Biochemistry
Year 1998
Volume 37
Pages 14386-93
Authors Thoma NH, Meier TW, Evans PR, Leadlay PF
Title Stabilization of radical intermediates by an active-site tyrosine residue in methylmalonyl-CoA mutase.
Related PDB 5req
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 98322359
PubMed ID 9655823
Journal Structure
Year 1998
Volume 6
Pages 711-20
Authors Mancia F, Evans PR
Title Conformational changes on substrate binding to methylmalonyl CoA mutase and new insights into the free radical mechanism.
Related PDB 2req 3req
Related UniProtKB P11652 P11653
[15]
Resource
Comments
Medline ID
PubMed ID 10563814
Journal Biochemistry
Year 1999
Volume 38
Pages 15287-94
Authors Chowdhury S, Banerjee R
Title Role of the dimethylbenzimidazole tail in the reaction catalyzed by coenzyme B12-dependent methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10387043
Journal Biochemistry
Year 1999
Volume 38
Pages 7999-8005
Authors Mancia F, Smith GA, Evans PR
Title Crystal structure of substrate complexes of methylmalonyl-CoA mutase.
Related PDB 4req 6req 7req
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 10551831
Journal J Biol Chem
Year 1999
Volume 274
Pages 32733-7
Authors Maiti N, Widjaja L, Banerjee R
Title Proton transfer from histidine 244 may facilitate the 1,2 rearrangement reaction in coenzyme B(12)-dependent methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10891081
Journal Biochemistry
Year 2000
Volume 39
Pages 7998-8006
Authors Chowdhury S, Banerjee R
Title Thermodynamic and kinetic characterization of Co-C bond homolysis catalyzed by coenzyme B(12)-dependent methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[19]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10924114
Journal Biochemistry
Year 2000
Volume 39
Pages 9213-21
Authors Thoma NH, Evans PR, Leadlay PF
Title Protection of radical intermediates at the active site of adenosylcobalamin-dependent methylmalonyl-CoA mutase.
Related PDB 1e1c
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11948881
Journal Chembiochem
Year 2001
Volume 2
Pages 919-22
Authors Wetmore SD, Smith DM, Radom L
Title Catalysis by mutants of methylmalonyl-CoA mutase: a theoretical rationalization for a change in the rate-determining step.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11031263
Journal J Biol Chem
Year 2001
Volume 276
Pages 1015-9
Authors Chowdhury S, Thomas MG, Escalante-Semerena JC, Banerjee R
Title The coenzyme b12 analog 5'-deoxyadenosylcobinamide-gdp supports catalysis by methylmalonyl-coa mutase in the absence of trans-ligand coordination.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 12196149
Journal Biochem Soc Trans
Year 2002
Volume 30
Pages 621-4
Authors Banerjee R, Vlasie M
Title Controlling the reactivity of radical intermediates by coenzyme B(12)-dependent methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11893736
Journal J Biol Chem
Year 2002
Volume 277
Pages 18523-7
Authors Vlasie M, Chowdhury S, Banerjee R
Title Importance of the histidine ligand to coenzyme B12 in the reaction catalyzed by methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 12797824
Journal Chem Rev
Year 2003
Volume 103
Pages 2083-94
Authors Banerjee R
Title Radical carbon skeleton rearrangements: catalysis by coenzyme B12-dependent mutases.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12569457
Journal Chemistry
Year 2003
Volume 9
Pages 652-60
Authors Weigl U, Heimberger M, Pierik AJ, Retey J
Title Synthesis of enantiomerically-pure [13C]aristeromycylcobalamin and its reactivity in dioldehydratase, glyceroldehydratase, ethanolamine ammonia-lyase and methylmalonyl-CoA mutase reactions.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12537507
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 1072-8
Authors Loferer MJ, Webb BM, Grant GH, Liedl KR
Title Energetic and stereochemical effects of the protein environment on substrate: a theoretical study of methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 12720457
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 5431-5
Authors Vlasie MD, Banerjee R
Title Tyrosine 89 accelerates Co-carbon bond homolysis in methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 15222752
Journal Biochemistry
Year 2004
Volume 43
Pages 8410-7
Authors Vlasie MD, Banerjee R
Title When a spectator turns killer: suicidal electron transfer from cobalamin in methylmalonyl-CoA mutase.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 15225058
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 8167-80
Authors Brooks AJ, Vlasie M, Banerjee R, Brunold TC
Title Spectroscopic and computational studies on the adenosylcobalamin-dependent methylmalonyl-CoA mutase: evaluation of enzymatic contributions to Co-C bond activation in the Co3+ ground state.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 15113202
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 5368-9
Authors Daublain P, Horner JH, Kuznetsov A, Newcomb M
Title Solvent polarity effects and limited acid catalysis in rearrangements of model radicals for the methylmalonyl-CoA mutase- and isobutyryl-CoA mutase-catalyzed isomerization reactions.
Related PDB
Related UniProtKB

Comments
This enzyme catalyzes radical reactions.

Created Updated
2005-05-27 2009-02-26