DB code: T00236

CATH domain 3.20.20.240 : TIM Barrel Catalytic domain
3.90.970.10 : Glutamate mutase, C-terminal domain
3.40.50.280 : Rossmann fold Catalytic domain
E.C. 5.4.99.1
CSA 1cb7
M-CSA 1cb7
MACiE M0063

CATH domain Related DB codes (homologues)
3.20.20.240 : TIM Barrel M00168
3.40.50.280 : Rossmann fold M00172 M00168

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
P80077 Methylaspartate mutase E chain
EC 5.4.99.1
Glutamate mutase subunit epsilon
PF06368 (Met_asp_mut_E)
[Graphical View]
P80078 Methylaspartate mutase S chain
EC 5.4.99.1
Glutamate mutase subunit sigma
PF02310 (B12-binding)
[Graphical View]
Q05509 Methylaspartate mutase E chain
EC 5.4.99.1
Glutamate mutase subunit epsilon
PF06368 (Met_asp_mut_E)
[Graphical View]
Q05488 Methylaspartate mutase S chain
EC 5.4.99.1
Glutamate mutase subunit sigma
PF02310 (B12-binding)
[Graphical View]

KEGG enzyme name
methylaspartate mutase
glutamate mutase
glutamic mutase
glutamic isomerase
glutamic acid mutase
glutamic acid isomerase
methylaspartic acid mutase
beta-methylaspartate-glutamate mutase
glutamate isomerase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P80077 GLME_CLOCO L-threo-3-methylaspartate = L-glutamate. Heterotetramer of 2 E subunits and 2 S subunits. Cobalamin.
P80078 MAMA_CLOCO L-threo-3-methylaspartate = L-glutamate. Heterotetramer of 2 E subunits and 2 S subunits. 5''-deoxy-5''-adenosyl-adeninylcobamide (pseudo-coenzyme B12).
Q05509 GLME_CLOTT L-threo-3-methylaspartate = L-glutamate. Possible heterotetramer, composed of two E chains and two S chains. E exists as a homodimer and S as a monomer. Cobalamin.
Q05488 MAMA_CLOTT L-threo-3-methylaspartate = L-glutamate. Heterotetramer of 2 E subunits and 2 S subunits. E exists as a homodimer and S as a monomer. 5''-deoxy-5''-adenosyl-adeninylcobamide (pseudo-coenzyme B12).

KEGG Pathways
Map code Pathways E.C.
MAP00660 C5-Branched dibasic acid metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00194 C03618 C00025
E.C.
Compound Cobamide coenzyme L-threo-3-Methylaspartate L-Glutamate
Type amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate,heavy metal,nucleoside,nucleotide amino acids,carboxyl group amino acids,carboxyl group
ChEBI 47980
 47980
 		16015
 16015
PubChem 440064
 440064
 		33032
 44272391
 88747398
 33032
 44272391
 88747398
1cb7B01 Unbound Analogue:TAR Unbound
1cb7D01 Unbound Analogue:TAR Unbound
1ccwB01 Unbound Analogue:TAR Unbound
1ccwD01 Unbound Analogue:TAR Unbound
1i9cB01 Bound:5AD Bound:3MD Bound:GLU
1i9cD01 Bound:5AD Bound:3MD Bound:GLU
1cb7B02 Unbound Unbound Unbound
1cb7D02 Unbound Unbound Unbound
1ccwB02 Unbound Unbound Unbound
1ccwD02 Unbound Unbound Unbound
1i9cB02 Unbound Unbound Unbound
1i9cD02 Unbound Unbound Unbound
1b1aA Unbound Unbound Unbound
1cb7A Analogue:COB Unbound Unbound
1cb7C Analogue:COB Unbound Unbound
1ccwA Analogue:CNC Unbound Unbound
1ccwC Analogue:CNC Unbound Unbound
1i9cA Bound:B12 Unbound Unbound
1i9cC Bound:B12 Unbound Unbound
1be1A Unbound Unbound Unbound
1fmfA Unbound Unbound Unbound
1id8A Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [14], [18], [28]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1cb7B01 ARG 100;GLU 171
1cb7D01 ARG 100;GLU 171
1ccwB01 ARG 100;GLU 171
1ccwD01 ARG 100;GLU 171
1i9cB01 ARG 100;GLU 171
1i9cD01 ARG 100;GLU 171
1cb7B02
1cb7D02
1ccwB02
1ccwD02
1i9cB02
1i9cD02
1b1aA ASP 14 HIS 16(Cobamide coenzyme binding)
1cb7A ASP 14 HIS 16(Cobamide coenzyme binding)
1cb7C ASP 14 HIS 16(Cobamide coenzyme binding)
1ccwA ASP 14 HIS 16(Cobamide coenzyme binding)
1ccwC ASP 14 HIS 16(Cobamide coenzyme binding)
1i9cA ASP 14 HIS 16(Cobamide coenzyme binding)
1i9cC ASP 14 HIS 16(Cobamide coenzyme binding)
1be1A ASP 14 HIS 16(Cobamide coenzyme binding)
1fmfA ASP 14 HIS 16(Cobamide coenzyme binding)
1id8A ASP 14 HIS 16(Cobamide coenzyme binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
Scheme 1, Scheme 2
[10]
Fig.2, p.11870-11872
[12]
Fig.1
[14]
Fig.1, p.897, p.899-900
[15]
Fig.5
[16]
Scheme 2
[17]
Scheme 1
[18]
Fig. 1, Fig.5, p.1147-1148
[20]
[25]
Fig.4, p.600-601
[26]
[28]
Fig.1, p.3243-3245
[29]
Fig.1, Fig.4, p.2690-2691

References
[1]
Resource
Comments
Medline ID
PubMed ID 1315276
Journal Eur J Biochem
Year 1992
Volume 205
Pages 759-65
Authors Leutbecher U, Bocher R, Linder D, Buckel W
Title Glutamate mutase from Clostridium cochlearium. Purification, cobamide content and stereospecific inhibitors.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1322827
Journal FEBS Lett
Year 1992
Volume 307
Pages 144-6
Authors Leutbecher U, Albracht SP, Buckel W
Title Identification of a paramagnetic species as an early intermediate in the coenzyme B12-dependent glutamate mutase reaction. A cob(II)amide?
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7712296
Journal Curr Opin Struct Biol
Year 1994
Volume 4
Pages 919-29
Authors Drennan CL, Matthews RG, Ludwig ML
Title Cobalamin-dependent methionine synthase: the structure of a methylcobalamin-binding fragment and implications for other B12-dependent enzymes.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7880251
Journal Eur J Biochem
Year 1994
Volume 226
Pages 577-85
Authors Zelder O, Beatrix B, Leutbecher U, Buckel W
Title Characterization of the coenzyme-B12-dependent glutamate mutase from Clostridium cochlearium produced in Escherichia coli.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7649266
Journal FEBS Lett
Year 1995
Volume 369
Pages 252-4
Authors Zelder O, Beatrix B, Kroll F, Buckel W
Title Coordination of a histidine residue of the protein-component S to the cobalt atom in coenzyme B12-dependent glutamate mutase from Clostridium cochlearium.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9003368
Journal Biochem J
Year 1996
Volume 320
Pages 825-30
Authors Holloway DE, Harding SE, Marsh EN
Title Adenosylcobalamin-dependent glutamate mutase: properties of a fusion protein in which the cobalamin-binding subunit is linked to the catalytic subunit.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8910568
Journal J Biol Chem
Year 1996
Volume 271
Pages 29121-5
Authors Holloway DE, Chen HP, Marsh EN
Title Carboxymethylation of MutS-cysteine-15 specifically inactivates adenosylcobalamin-dependent glutamate mutase. Examination of the role of this residue in coenzyme-binding and catalysis.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9201933
Journal Biochemistry
Year 1997
Volume 36
Pages 7884-9
Authors Chen HP, Marsh EN
Title How enzymes control the reactivity of adenosylcobalamin: effect on coenzyme binding and catalysis of mutations in the conserved histidine-aspartate pair of glutamate mutase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9521732
Journal Biochemistry
Year 1998
Volume 37
Pages 4105-13
Authors Bothe H, Darley DJ, Albracht SP, Gerfen GJ, Golding BT, Buckel W
Title Identification of the 4-glutamyl radical as an intermediate in the carbon skeleton rearrangement catalyzed by coenzyme B12-dependent glutamate mutase from Clostridium cochlearium.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 9718309
Journal Biochemistry
Year 1998
Volume 37
Pages 11864-72
Authors Marsh EN, Ballou DP
Title Coupling of cobalt-carbon bond homolysis and hydrogen atom abstraction in adenosylcobalamin-dependent glutamate mutase.
Related PDB
Related UniProtKB
[11]
Resource
Comments STRUCTURE BY NMR.
Medline ID
PubMed ID 9739092
Journal Structure
Year 1998
Volume 6
Pages 1021-33
Authors Tollinger M, Konrat R, Hilbert BH, Marsh EN, Krautler B
Title How a protein prepares for B12 binding: structure and dynamics of the B12-binding subunit of glutamate mutase from Clostridium tetanomorphum.
Related PDB 1be1
Related UniProtKB Q05488
[12]
Resource
Comments
Medline ID
PubMed ID 10521275
Journal Biochemistry
Year 1999
Volume 38
Pages 13684-91
Authors Chih HW, Marsh EN
Title Pre-steady-state kinetic investigation of intermediates in the reaction catalyzed by adenosylcobalamin-dependent glutamate mutase.
Related PDB
Related UniProtKB
[13]
Resource
Comments NMR spectroscopy
Medline ID
PubMed ID 10429202
Journal Eur J Biochem
Year 1999
Volume 263
Pages 178-88
Authors Hoffmann B, Konrat R, Bothe H, Buckel W, Krautler B
Title Structure and dynamics of the B12-binding subunit of glutamate mutase from Clostridium cochlearium.
Related PDB 1b1a
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
Medline ID 99404935
PubMed ID 10467146
Journal Structure Fold Des
Year 1999
Volume 7
Pages 891-902
Authors Reitzer R, Gruber K, Jogl G, Wagner UG, Bothe H, Buckel W, Kratky C
Title Glutamate mutase from Clostridium cochlearium: the structure of a coenzyme B12-dependent enzyme provides new mechanistic insights.
Related PDB 1cb7 1ccw
Related UniProtKB P80077
[15]
Resource
Comments
Medline ID
PubMed ID 10956023
Journal Biochemistry
Year 2000
Volume 39
Pages 10340-6
Authors Roymoulik I, Moon N, Dunham WR, Ballou DP, Marsh EN
Title Rearrangement of L-2-hydroxyglutarate to L-threo-3-methylmalate catalyzed by adenosylcobalamin-dependent glutamate mutase.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11592143
Journal Angew Chem Int Ed Engl
Year 2001
Volume 40
Pages 3377-3380
Authors Gruber K, Reitzer R, Kratky C
Title Radical Shuttling in a Protein: Ribose Pseudorotation Controls Alkyl-Radical Transfer in the Coenzyme B(12) Dependent Enzyme Glutamate Mutase.
Related PDB 1i9c
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 11256957
Journal Biochem J
Year 2001
Volume 355
Pages 131-7
Authors Huhta MS, Chen HP, Hemann C, Hille CR, Marsh EN
Title Protein-coenzyme interactions in adenosylcobalamin-dependent glutamate mutase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 11755393
Journal Chem Biol
Year 2001
Volume 8
Pages 1143-9
Authors Madhavapeddi P, Marsh EN
Title The role of the active site glutamate in the rearrangement of glutamate to 3-methylaspartate catalyzed by adenosylcobalamin-dependent glutamate mutase.
Related PDB
Related UniProtKB
[19]
Resource
Comments NMR spectroscopy
Medline ID
PubMed ID 11828501
Journal Chembiochem
Year 2001
Volume 2
Pages 643-55
Authors Hoffmann B, Tollinger M, Konrat R, Huhta M, Marsh EN, Krautler B
Title A protein pre-organized to trap the nucleotide moiety of coenzyme B(12): refined solution structure of the B(12)-binding subunit of glutamate mutase from Clostridium tetanomorphum.
Related PDB 1fmf
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 11506551
Journal J Am Chem Soc
Year 2001
Volume 123
Pages 7963-72
Authors Wetmore SD, Smith DM, Golding BT, Radom L
Title Interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate: a distinctive B(12)-dependent carbon-skeleton rearrangement.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11727974
Journal J Biomol NMR
Year 2001
Volume 21
Pages 107-16
Authors Eichmuller C, Schuler W, Konrat R, Krautler B
Title Simultaneous measurement of intra- and intermolecular NOEs in differentially labeled protein-ligand complexes.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11519744
Journal J Biomol NMR
Year 2001
Volume 20
Pages 195-202
Authors Eichmuller C, Tollinger M, Krautler B, Konrat R
Title Mapping the ligand binding site at protein side-chains in protein-ligand complexes through NOE difference spectroscopy.
Related PDB
Related UniProtKB
[23]
Resource
Comments NMR spectroscopy
Medline ID
PubMed ID 11397096
Journal J Mol Biol
Year 2001
Volume 309
Pages 777-91
Authors Tollinger M, Eichmuller C, Konrat R, Huhta MS, Marsh EN, Krautler B
Title The B(12)-binding subunit of glutamate mutase from Clostridium tetanomorphum traps the nucleotide moiety of coenzyme B(12).
Related PDB 1id8
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11863459
Journal Biochemistry
Year 2002
Volume 41
Pages 3200-6
Authors Huhta MS, Ciceri D, Golding BT, Marsh EN
Title A novel reaction between adenosylcobalamin and 2-methyleneglutarate catalyzed by glutamate mutase.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12413543
Journal Curr Opin Chem Biol
Year 2002
Volume 6
Pages 598-603
Authors Gruber K, Kratky C
Title Coenzyme B(12) dependent glutamate mutase.
Related PDB
Related UniProtKB
[26]
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
[27]
Resource
Comments
Medline ID
PubMed ID 14979711
Journal Biochemistry
Year 2004
Volume 43
Pages 2155-8
Authors Cheng MC, Marsh EN
Title Pre-steady-state measurement of intrinsic secondary tritium isotope effects associated with the homolysis of adenosylcobalamin and the formation of 5'-deoxyadensosine in glutamate mutase.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 15023074
Journal Biochemistry
Year 2004
Volume 43
Pages 3238-45
Authors Xia L, Ballou DP, Marsh EN
Title Role of Arg100 in the active site of adenosylcobalamin-dependent glutamate mutase.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 15709782
Journal Biochemistry
Year 2005
Volume 44
Pages 2686-91
Authors Cheng MC, Marsh EN
Title Isotope effects for deuterium transfer between substrate and coenzyme in adenosylcobalamin-dependent glutamate mutase.
Related PDB
Related UniProtKB

Comments
According to the literature, this enzyme catalyzes "fragmentation" and "recombination" by radical transfer from Cobamide coenzyme (or Vitamine B12).

Created Updated
2005-05-20 2009-03-10