DB code: T00086

CATH domain 1.10.275.10 : Fumarase C; Chain B, domain 1
1.20.200.10 : Fumarase C; Chain A, domain 2 Catalytic domain
1.10.40.30 : Ribonucleotide Reductase Protein R1; domain 1
E.C. 4.2.1.2
CSA 1fuq
M-CSA 1fuq
MACiE

CATH domain Related DB codes (homologues)
1.10.275.10 : Fumarase C; Chain B, domain 1 D00267 T00092 T00094 T00095
1.10.40.30 : Ribonucleotide Reductase Protein R1; domain 1 T00092 T00094 T00095
1.20.200.10 : Fumarase C; Chain A, domain 2 D00267 T00092 T00094 T00095

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P05042 Fumarate hydratase class II
Fumarase C
EC 4.2.1.2
Iron-independent fumarase
NP_416128.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_489874.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF10415 (FumaraseC_C)
PF00206 (Lyase_1)
[Graphical View]
O66271 Fumarate hydratase class II
Fumarase C
EC 4.2.1.2
YP_004165.1 (Protein)
NC_005835.1 (DNA/RNA sequence)
PF10415 (FumaraseC_C)
PF00206 (Lyase_1)
[Graphical View]
P08417 Fumarate hydratase, mitochondrial
Fumarase
EC 4.2.1.2
NP_015061.1 (Protein)
NM_001184076.1 (DNA/RNA sequence)
PF10415 (FumaraseC_C)
PF00206 (Lyase_1)
[Graphical View]

KEGG enzyme name
fumarate hydratase
fumarase
L-malate hydro-lyase
(S)-malate hydro-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P05042 FUMC_ECOLI (S)-malate = fumarate + H(2)O. Homotetramer. Cytoplasm.
O66271 FUMC_THET2 (S)-malate = fumarate + H(2)O. Homotetramer (By similarity). Cytoplasm (By similarity).
P08417 FUMH_YEAST (S)-malate = fumarate + H(2)O. Homotetramer. Mitochondrion matrix. Cytoplasm. Note=Both fumarases are encoded by a single nuclear gene.

KEGG Pathways
Map code Pathways E.C.
MAP00020 Citrate cycle (TCA cycle)
MAP00720 Reductive carboxylate cycle (CO2 fixation)

Compound table
Substrates Products Intermediates
KEGG-id C00149 C00122 C00001
E.C.
Compound (S)-Malate Fumarate H2O
Type carbohydrate,carboxyl group carboxyl group H2O
ChEBI 30797
18012
15377
PubChem 222656
21883788
444972
22247451
962
1fuoA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
1fuoB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
1fupA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fupB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuqA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
1fuqB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
1furA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1furB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1kq7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
1kq7B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
1yfeA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
2fusA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
2fusB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:CIT Unbound
1vdkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1vdkB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1yfmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuoA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuoB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fupA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fupB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuqA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuqB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1furA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1furB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1kq7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1kq7B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1yfeA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
2fusA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
2fusB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1vdkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1vdkB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1yfmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuoA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuoB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fupA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fupB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuqA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1fuqB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1furA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1furB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1kq7A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1kq7B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1yfeA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
2fusA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
2fusB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1vdkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1vdkB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1yfmA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P05042, P08417

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1fuoA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fuoB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fupA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fupB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fuqA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fuqB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1furA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1furB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1kq7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1kq7B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1yfeA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2fusA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant H129N
2fusB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant H129N
1vdkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1vdkB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1yfmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fuoA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;SER 318;LYS 324;GLU 331
1fuoB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;;LYS 324;GLU 331 invisible 317-320
1fupA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;SER 318;LYS 324;GLU 331
1fupB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;;LYS 324;GLU 331 invisible 317-320
1fuqA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;SER 318;LYS 324;GLU 331
1fuqB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;;LYS 324;GLU 331 invisible 317-320
1furA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ;SER 318;LYS 324;GLU 331 mutant H188N
1furB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ; ;LYS 324;GLU 331 mutant H188N, invisible 317-320
1kq7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;SER 318;LYS 324;GLU 331 mutant E315Q
1kq7B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;;LYS 324;GLU 331 mutant E315Q, invisible 317-320
1yfeA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;SER 318;LYS 324;GLU 331
2fusA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;SER 318;LYS 324;GLU 331
2fusB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;;LYS 324;GLU 331 invisible 317-320
1vdkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;SER 318;LYS 324;GLU 331
1vdkB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 188;;LYS 324;GLU 331 invisible 317-320
1yfmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 213;SER 343;LYS 349;GLU 356 mutant K289R
1fuoA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fuoB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fupA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fupB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fuqA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1fuqB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1furA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1furB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1kq7A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1kq7B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1yfeA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2fusA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2fusB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1vdkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1vdkB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1yfmA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
Fig.1, p.660-661 2
[13]
[16]
p.437-438
[20]
[21]
p.1399

References
[1]
Resource
Comments
Medline ID
PubMed ID 4365214
Journal Mol Cell Biochem
Year 1974
Volume 3
Pages 207-11
Authors Wolfenden R
Title Enzyme catalysis: conflicting requirements of substrate access and transition state affinity.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 893568
Journal J Chem Educ
Year 1977
Volume 54
Pages 515-6
Authors Kasperek GJ, Pratt RF
Title The fumarase reaction.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7287666
Journal J Biochem (Tokyo)
Year 1981
Volume 89
Pages 1923-31
Authors Kobayashi K, Yamanishi T, Tuboi S
Title Physicochemical, catalytic, and immunochemical properties of fumarases crystallized separately from mitochondrial and cytosolic fractions of rat liver.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 7138916
Journal Biochim Biophys Acta
Year 1982
Volume 721
Pages 191-200
Authors Simpson RJ, Brindle KM, Campbell ID
Title Spin ECHO proton NMR studies of the metabolism of malate and fumarate in human erythrocytes. Dependence on free NAD levels.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 3771571
Journal J Biol Chem
Year 1986
Volume 261
Pages 15183-5
Authors Sacchettini JC, Meininger T, Roderick S, Banaszak LJ
Title Purification, crystallization, and preliminary X-ray data for porcine fumarase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 1327137
Journal Biochemistry
Year 1992
Volume 31
Pages 9993-9
Authors Rose IA, Warms JV, Kuo DJ
Title Proton transfer in catalysis by fumarase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 1633200
Journal Biochim Biophys Acta
Year 1992
Volume 1122
Pages 85-92
Authors Keruchenko JS, Keruchenko ID, Gladilin KL, Zaitsev VN, Chirgadze NY
Title Purification, characterization and preliminary X-ray study of fumarase from Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8496960
Journal J Mol Biol
Year 1993
Volume 231
Pages 141-4
Authors Weaver TM, Levitt DG, Banaszak LJ
Title Purification and crystallization of fumarase C from Escherichia coli.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8031132
Journal Arch Biochem Biophys
Year 1994
Volume 312
Pages 227-33
Authors Rebholz KL, Northrop DB
Title Kinetics of enzymes with iso-mechanisms: dead-end inhibition of fumarase and carbonic anhydrase II.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7552727
Journal Nat Struct Biol
Year 1995
Volume 2
Pages 654-62
Authors Weaver TM, Levitt DG, Donnelly MI, Stevens PP, Banaszak LJ
Title The multisubunit active site of fumarase C from Escherichia coli.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 7624773
Journal Science
Year 1995
Volume 269
Pages 527-9
Authors Mohrig JR, Moerke KA, Cloutier DL, Lane BD, Person EC, Onasch TB
Title Importance of historical contingency in the stereochemistry of hydratase-dehydratase enzymes.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8593099
Journal Arch Microbiol
Year 1996
Volume 165
Pages 126-31
Authors Van Kuijk BL, Van Loo ND, Arendsen AF, Hagen WR, Stams AJ
Title Purification and characterization of fumarase from the syntrophic propionate-oxidizing bacterium strain MPOB.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID 97065812
PubMed ID 8909293
Journal Biochemistry
Year 1996
Volume 35
Pages 13955-65
Authors Weaver T, Banaszak L
Title Crystallographic studies of the catalytic and a second site in fumarase C from Escherichia coli.
Related PDB 1fuo 1fup 1fuq
Related UniProtKB P05042
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
Medline ID 97253450
PubMed ID 9098893
Journal Protein Sci
Year 1997
Volume 6
Pages 834-42
Authors Weaver T, Lees M, Banaszak L
Title Mutations of fumarase that distinguish between the active site and a nearby dicarboxylic acid binding site.
Related PDB 1fur 2fus
Related UniProtKB P05042
[15]
Resource
Comments
Medline ID
PubMed ID 9822627
Journal J Biol Chem
Year 1998
Volume 273
Pages 31661-9
Authors Beeckmans S, Van Driessche E
Title Pig heart fumarase contains two distinct substrate-binding sites differing in affinity.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID 98332745
PubMed ID 9665847
Journal J Mol Biol
Year 1998
Volume 280
Pages 431-42
Authors Weaver T, Lees M, Zaitsev V, Zaitseva I, Duke E, Lindley P, McSweeny S, Svensson A, Keruchenko J, Keruchenko I, Gladilin K, Banaszak L
Title Crystal structures of native and recombinant yeast fumarase.
Related PDB 1yfm
Related UniProtKB P08417
[17]
Resource
Comments
Medline ID
PubMed ID 10739264
Journal Protein Sci
Year 2000
Volume 9
Pages 201-6
Authors Weaver TM
Title The pi-helix translates structure into function.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 12052057
Journal Biotechnol Prog
Year 2002
Volume 18
Pages 445-50
Authors Bressler E, Pines O, Goldberg I, Braun S
Title Conversion of fumaric acid to L-malic by sol-gel immobilized Saccharomyces cerevisiae in a supported liquid membrane bioreactor.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 12021453
Journal Protein Sci
Year 2002
Volume 11
Pages 1552-7
Authors Estevez M, Skarda J, Spencer J, Banaszak L, Weaver TM
Title X-ray crystallographic and kinetic correlation of a clinically observed human fumarase mutation.
Related PDB 1kq7
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 14990798
Journal Proc Natl Acad Sci U S A
Year 2004
Volume 101
Pages 3393-7
Authors Rose IA, Weaver TM
Title The role of the allosteric B site in the fumarase reaction.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 16204892
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 1395-401
Authors Weaver T
Title Structure of free fumarase C from Escherichia coli.
Related PDB 1yfe
Related UniProtKB

Comments
This enzyme has got two binding sites for malate, site A and site B. The site A is close to the catalytic site, whereas the site B seems to be allosteric site. Although the PDB structures, 1fuo, 1fup, 1fur and 1kq7, bind malate (MLT), they are bound to the site B.
This enzyme is homologous to argininosuccinate lyase (T00094 in EzCatDB), and the catalytic residues are conserved. Thus, the reaction might be similar to that of the homologue.

Created Updated
2004-06-02 2009-02-26