EzCatDB: T00086
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DB codeT00086
CATH domainDomain 11.10.275.10 : Fumarase C; Chain B, domain 1
Domain 21.20.200.10 : Fumarase C; Chain A, domain 2Catalytic domain
Domain 31.10.40.30 : Ribonucleotide Reductase Protein R1; domain 1
E.C.4.2.1.2
CSA1fuq

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

Enzyme Name
UniProtKBKEGG

P05042O66271P08417
Protein nameFumarate hydratase class IIFumarate hydratase class IIFumarate hydratase, mitochondrialfumarate hydratase
fumarase
L-malate hydro-lyase
(S)-malate hydro-lyase
SynonymsFumarase C
EC 4.2.1.2
Iron-independent fumarase
Fumarase C
EC 4.2.1.2
Fumarase
EC 4.2.1.2
RefSeqNP_416128.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_489874.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
YP_004165.1 (Protein)
NC_005835.1 (DNA/RNA sequence)
NP_015061.1 (Protein)
NM_001184076.1 (DNA/RNA sequence)
PfamPF10415 (FumaraseC_C)
PF00206 (Lyase_1)
[Graphical view]
PF10415 (FumaraseC_C)
PF00206 (Lyase_1)
[Graphical view]
PF10415 (FumaraseC_C)
PF00206 (Lyase_1)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00020Citrate cycle (TCA cycle)
MAP00720Reductive carboxylate cycle (CO2 fixation)

UniProtKB:Accession NumberP05042O66271P08417
Entry nameFUMC_ECOLIFUMC_THET2FUMH_YEAST
Activity(S)-malate = fumarate + H(2)O.(S)-malate = fumarate + H(2)O.(S)-malate = fumarate + H(2)O.
SubunitHomotetramer.Homotetramer (By similarity).Homotetramer.
Subcellular locationCytoplasm.Cytoplasm (By similarity).Mitochondrion matrix. Cytoplasm. Note=Both fumarases are encoded by a single nuclear gene.
Cofactor



Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00149C00122C00001
Compound(S)-MalateFumarateH2O
Typecarbohydrate,carboxyl groupcarboxyl groupH2O
ChEBI30797
18012
15377
PubChem222656
444972
21883788
962
22247451
           
1fuoA01Analogue:CITUnbound 
1fuoB01Analogue:CITUnbound 
1fupA01UnboundUnbound 
1fupB01UnboundUnbound 
1fuqA01Analogue:CITUnbound 
1fuqB01Analogue:CITUnbound 
1furA01UnboundUnbound 
1furB01UnboundUnbound 
1kq7A01Analogue:CITUnbound 
1kq7B01Analogue:CITUnbound 
1yfeA01UnboundUnbound 
2fusA01Analogue:CITUnbound 
2fusB01Analogue:CITUnbound 
1vdkA01UnboundUnbound 
1vdkB01UnboundUnbound 
1yfmA01UnboundUnbound 
1fuoA02UnboundUnbound 
1fuoB02UnboundUnbound 
1fupA02UnboundUnbound 
1fupB02UnboundUnbound 
1fuqA02UnboundUnbound 
1fuqB02UnboundUnbound 
1furA02UnboundUnbound 
1furB02UnboundUnbound 
1kq7A02UnboundUnbound 
1kq7B02UnboundUnbound 
1yfeA02UnboundUnbound 
2fusA02UnboundUnbound 
2fusB02UnboundUnbound 
1vdkA02UnboundUnbound 
1vdkB02UnboundUnbound 
1yfmA02UnboundUnbound 
1fuoA03UnboundUnbound 
1fuoB03UnboundUnbound 
1fupA03UnboundUnbound 
1fupB03UnboundUnbound 
1fuqA03UnboundUnbound 
1fuqB03UnboundUnbound 
1furA03UnboundUnbound 
1furB03UnboundUnbound 
1kq7A03UnboundUnbound 
1kq7B03UnboundUnbound 
1yfeA03UnboundUnbound 
2fusA03UnboundUnbound 
2fusB03UnboundUnbound 
1vdkA03UnboundUnbound 
1vdkB03UnboundUnbound 
1yfmA03UnboundUnbound 

Active-site residues
resource
Swiss-prot;P05042, P08417
pdbCatalytic residuescomment
          
1fuoA01               
 
1fuoB01               
 
1fupA01               
 
1fupB01               
 
1fuqA01               
 
1fuqB01               
 
1furA01               
 
1furB01               
 
1kq7A01               
 
1kq7B01               
 
1yfeA01               
 
2fusA01               
mutant H129N
2fusB01               
mutant H129N
1vdkA01               
 
1vdkB01               
 
1yfmA01               
 
1fuoA02HIS 188;SER 318;LYS 324;GLU 331
 
1fuoB02HIS 188;       ;LYS 324;GLU 331
invisible 317-320
1fupA02HIS 188;SER 318;LYS 324;GLU 331
 
1fupB02HIS 188;       ;LYS 324;GLU 331
invisible 317-320
1fuqA02HIS 188;SER 318;LYS 324;GLU 331
 
1fuqB02HIS 188;       ;LYS 324;GLU 331
invisible 317-320
1furA02       ;SER 318;LYS 324;GLU 331
mutant H188N
1furB02       ;       ;LYS 324;GLU 331
mutant H188N, invisible 317-320
1kq7A02HIS 188;SER 318;LYS 324;GLU 331
mutant E315Q
1kq7B02HIS 188;       ;LYS 324;GLU 331
mutant E315Q, invisible 317-320
1yfeA02HIS 188;SER 318;LYS 324;GLU 331
 
2fusA02HIS 188;SER 318;LYS 324;GLU 331
 
2fusB02HIS 188;       ;LYS 324;GLU 331
invisible 317-320
1vdkA02HIS 188;SER 318;LYS 324;GLU 331
 
1vdkB02HIS 188;       ;LYS 324;GLU 331
invisible 317-320
1yfmA02HIS 213;SER 343;LYS 349;GLU 356
mutant K289R
1fuoA03 
 
1fuoB03 
 
1fupA03 
 
1fupB03 
 
1fuqA03 
 
1fuqB03 
 
1furA03 
 
1furB03 
 
1kq7A03 
 
1kq7B03 
 
1yfeA03 
 
2fusA03 
 
2fusB03 
 
1vdkA03 
 
1vdkB03 
 
1yfmA03 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]Fig.1, p.660-6612
[13]

[16]p.437-438
[20]

[21]p.1399

references
[1]
PubMed ID4365214
JournalMol Cell Biochem
Year1974
Volume3
Pages207-11
AuthorsWolfenden R
TitleEnzyme catalysis: conflicting requirements of substrate access and transition state affinity.
[2]
PubMed ID893568
JournalJ Chem Educ
Year1977
Volume54
Pages515-6
AuthorsKasperek GJ, Pratt RF
TitleThe fumarase reaction.
[3]
PubMed ID7287666
JournalJ Biochem (Tokyo)
Year1981
Volume89
Pages1923-31
AuthorsKobayashi K, Yamanishi T, Tuboi S
TitlePhysicochemical, catalytic, and immunochemical properties of fumarases crystallized separately from mitochondrial and cytosolic fractions of rat liver.
[4]
PubMed ID7138916
JournalBiochim Biophys Acta
Year1982
Volume721
Pages191-200
AuthorsSimpson RJ, Brindle KM, Campbell ID
TitleSpin ECHO proton NMR studies of the metabolism of malate and fumarate in human erythrocytes. Dependence on free NAD levels.
[5]
PubMed ID3771571
JournalJ Biol Chem
Year1986
Volume261
Pages15183-5
AuthorsSacchettini JC, Meininger T, Roderick S, Banaszak LJ
TitlePurification, crystallization, and preliminary X-ray data for porcine fumarase.
[6]
PubMed ID1327137
JournalBiochemistry
Year1992
Volume31
Pages9993-9
AuthorsRose IA, Warms JV, Kuo DJ
TitleProton transfer in catalysis by fumarase.
[7]
PubMed ID1633200
JournalBiochim Biophys Acta
Year1992
Volume1122
Pages85-92
AuthorsKeruchenko JS, Keruchenko ID, Gladilin KL, Zaitsev VN, Chirgadze NY
TitlePurification, characterization and preliminary X-ray study of fumarase from Saccharomyces cerevisiae.
[8]
PubMed ID8496960
JournalJ Mol Biol
Year1993
Volume231
Pages141-4
AuthorsWeaver TM, Levitt DG, Banaszak LJ
TitlePurification and crystallization of fumarase C from Escherichia coli.
[9]
PubMed ID8031132
JournalArch Biochem Biophys
Year1994
Volume312
Pages227-33
AuthorsRebholz KL, Northrop DB
TitleKinetics of enzymes with iso-mechanisms: dead-end inhibition of fumarase and carbonic anhydrase II.
[10]
PubMed ID7552727
JournalNat Struct Biol
Year1995
Volume2
Pages654-62
AuthorsWeaver TM, Levitt DG, Donnelly MI, Stevens PP, Banaszak LJ
TitleThe multisubunit active site of fumarase C from Escherichia coli.
[11]
PubMed ID7624773
JournalScience
Year1995
Volume269
Pages527-9
AuthorsMohrig JR, Moerke KA, Cloutier DL, Lane BD, Person EC, Onasch TB
TitleImportance of historical contingency in the stereochemistry of hydratase-dehydratase enzymes.
[12]
PubMed ID8593099
JournalArch Microbiol
Year1996
Volume165
Pages126-31
AuthorsVan Kuijk BL, Van Loo ND, Arendsen AF, Hagen WR, Stams AJ
TitlePurification and characterization of fumarase from the syntrophic propionate-oxidizing bacterium strain MPOB.
[13]
CommentsX-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
Medline ID97065812
PubMed ID8909293
JournalBiochemistry
Year1996
Volume35
Pages13955-65
AuthorsWeaver T, Banaszak L
TitleCrystallographic studies of the catalytic and a second site in fumarase C from Escherichia coli.
Related PDB1fuo,1fup,1fuq
Related UniProtKBP05042
[14]
CommentsX-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
Medline ID97253450
PubMed ID9098893
JournalProtein Sci
Year1997
Volume6
Pages834-42
AuthorsWeaver T, Lees M, Banaszak L
TitleMutations of fumarase that distinguish between the active site and a nearby dicarboxylic acid binding site.
Related PDB1fur,2fus
Related UniProtKBP05042
[15]
PubMed ID9822627
JournalJ Biol Chem
Year1998
Volume273
Pages31661-9
AuthorsBeeckmans S, Van Driessche E
TitlePig heart fumarase contains two distinct substrate-binding sites differing in affinity.
[16]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
Medline ID98332745
PubMed ID9665847
JournalJ Mol Biol
Year1998
Volume280
Pages431-42
AuthorsWeaver T, Lees M, Zaitsev V, Zaitseva I, Duke E, Lindley P, McSweeny S, Svensson A, Keruchenko J, Keruchenko I, Gladilin K, Banaszak L
TitleCrystal structures of native and recombinant yeast fumarase.
Related PDB1yfm
Related UniProtKBP08417
[17]
PubMed ID10739264
JournalProtein Sci
Year2000
Volume9
Pages201-6
AuthorsWeaver TM
TitleThe pi-helix translates structure into function.
[18]
PubMed ID12052057
JournalBiotechnol Prog
Year2002
Volume18
Pages445-50
AuthorsBressler E, Pines O, Goldberg I, Braun S
TitleConversion of fumaric acid to L-malic by sol-gel immobilized Saccharomyces cerevisiae in a supported liquid membrane bioreactor.
[19]
PubMed ID12021453
JournalProtein Sci
Year2002
Volume11
Pages1552-7
AuthorsEstevez M, Skarda J, Spencer J, Banaszak L, Weaver TM
TitleX-ray crystallographic and kinetic correlation of a clinically observed human fumarase mutation.
Related PDB1kq7
[20]
PubMed ID14990798
JournalProc Natl Acad Sci U S A
Year2004
Volume101
Pages3393-7
AuthorsRose IA, Weaver TM
TitleThe role of the allosteric B site in the fumarase reaction.
[21]
PubMed ID16204892
JournalActa Crystallogr D Biol Crystallogr
Year2005
Volume61
Pages1395-401
AuthorsWeaver T
TitleStructure of free fumarase C from Escherichia coli.
Related PDB1yfe

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.

createdupdated
2004-06-022009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
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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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