EzCatDB: D00014

DB codeD00014
CATH domainDomain 13.10.120.10
Domain 23.20.20.70Catalytic domain
E.C.1.1.2.3
CSA1fcb
MACiEM0102

CATH domainRelated DB codes (homologues)
3.10.120.10T00018
3.20.20.70S00215,S00217,S00218,S00219,S00532,S00198,S00220,S00745,S00537,S00538,S00539,S00826,S00841,S00235,S00239,S00240,S00243,S00244,S00199,S00200,S00201,S00221,S00222,S00847,S00224,S00225,S00226,D00029,M00141,T00015,T00239,D00664,D00665,D00804,D00863,T00089

Enzyme Name
Swiss-protKEGG

P00175
Protein nameCytochrome b2, mitochondrialL-lactate dehydrogenase (cytochrome)
lactic acid dehydrogenase
cytochrome b2 (flavin-free derivative of flavocytochrome b2)
flavocytochrome b2
L-lactate cytochrome c reductase
L(+)-lactate:cytochrome c oxidoreductase
dehydrogenase, lactate (cytochrome)
L-lactate cytochrome c oxidoreductase
lactate dehydrogenase (cytochrome)
lactic cytochrome c reductase
SynonymsEC 1.1.2.3
L-lactate dehydrogenase [Cytochrome]
L-lactate ferricytochrome C oxidoreductase
L-LCR

KEGG pathways
MAP codePathways
MAP00620Pyruvate metabolism

Swiss-prot:Accession NumberP00175
Entry nameCYB2_YEAST
Activity(S)-lactate + 2 ferricytochrome c = pyruvate + 2 ferrocytochrome c + 2 H(+).
SubunitHomotetramer.
Subcellular locationMitochondrion intermembrane space.
CofactorFMN.,Protoheme IX groups.


CofactorsSubstratesProducts
KEGG-idC00061C00032C00186C00125C00022C00126
CompoundFMNProtoheme(S)-LactateFerricytochrome cPyruvateFerrocytochrome c
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ionaromatic ring (with nitrogen atoms),carboxyl group,heavy metalcarbohydrate,carboxyl groupamide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide groupcarbohydrate,carboxyl groupamide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide group
1fcbA01UnboundBound:HEMUnboundUnboundUnboundUnbound
1lcoA01UnboundBound:HEMUnboundUnboundUnboundUnbound
1ldcA01UnboundBound:HEMUnboundUnboundUnboundUnbound
1ltdA01UnboundBound:HEMUnboundUnboundUnboundUnbound
1fcbA02Bound:FMNUnboundUnboundUnboundUnboundUnbound
1fcbBBound:FMNUnboundUnboundUnboundAnalogue:PYRUnbound
1lcoA02Bound:FMNUnboundUnboundUnboundAnalogue:PPYUnbound
1lcoBBound:FMNUnboundUnboundUnboundAnalogue:PPYUnbound
1ldcA02Bound:FMNUnboundUnboundUnboundAnalogue:PYRUnbound
1ldcBBound:FMNUnboundUnboundUnboundAnalogue:PYRUnbound
1ltdA02Bound:FMNUnboundUnboundUnboundUnboundUnbound
1ltdBAnalogue:FMN-SO3UnboundUnboundUnboundUnboundUnbound
1qcwA01Analogue:FNSUnboundUnboundUnboundUnboundUnbound
1qcwB01Analogue:FNSUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P00175 & literature [6]
pdbCatalytic residuesCofactor-binding residuescomment
1fcbA01
HIS 43;HIS 66(Fe binding)

1lcoA01
HIS 43;HIS 66(Fe bindind)

1ldcA01
HIS 43;HIS 66(Fe binding)

1ltdA01
HIS 43;HIS 66(Fe binding)

1fcbA02TYR 254;ASP 282;HIS 373;ARG 376


1fcbBTYR 254;ASP 282;HIS 373;ARG 376


1lcoA02TYR 254;ASP 282;HIS 373;ARG 376

mutant Y143F
1lcoBTYR 254;ASP 282;HIS 373;ARG 376

mutant Y143F
1ldcA02TYR 254;ASP 282;HIS 373;ARG 376

mutant Y143F
1ldcBTYR 254;ASP 282;HIS 373;ARG 376

mutant Y143F
1ltdA02TYR 254;ASP 282;HIS 373;ARG 376


1ltdBTYR 254;ASP 282;HIS 373;ARG 376


1qcwA01TYR 254;ASP 282;HIS 373;ARG 376

mutant R289K;P304F,invisible F304
1qcwB01TYR 254;ASP 282;HIS 373;ARG 376

mutant R289K;P304F,invisible F304

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Scheme 3, p.350
[2]p.2632-2833
[3]p.7370
[6]Fig.1, Scheme I, p.6399
[7]Fig.17, p.853, p.856-857
[8]Fig.1, Scheme 1, Scheme 2, p.192
[11]Fig.1, Fig.4, p.805
[12]Fig.1
[14]Fig.2, p.9849
[15]Fig.5, p.626-629
[16]Fig.12
[18]p.6347-6349, Fig.1
[19]Fig.1, p.8593
[26]p.5165-5166
[27]Scheme 23
[28]Fig.1p.4925-4926

references
[1]
PubMed ID6386468
JournalEur J Biochem
Year1984
Volume144
Pages345-51
AuthorsUrban P, Lederer F
TitleBaker's yeast flavocytochrome b2. A mechanistic study of the dehydrohalogenation reaction.
[2]
PubMed ID3554243
JournalProc Natl Acad Sci U S A
Year1987
Volume84
Pages2629-33
AuthorsXia ZX, Shamala N, Bethge PH, Lim LW, Bellamy HD, Xuong NH, Lederer F, Mathews FS
TitleThree-dimensional structure of flavocytochrome b2 from baker's yeast at 3.0-A resolution.
[3]
PubMed ID3061453
JournalBiochemistry
Year1988
Volume27
Pages7365-71
AuthorsUrban P, Chirat I, Lederer F
TitleRat kidney L-2-hydroxyacid oxidase. Structural and mechanistic comparison with flavocytochrome b2 from baker's yeast.
[4]
PubMed ID3058697
JournalJ Biol Chem
Year1988
Volume263
Pages19278-81
AuthorsTegoni M, Mathews FS
TitleCrystallographic study of the complex between sulfite and bakers' yeast flavocytochrome b2.
[5]
PubMed ID2688640
JournalBiochem J
Year1989
Volume263
Pages973-6
AuthorsBlack MT, Gunn FJ, Chapman SK, Reid GA
TitleStructural basis for the kinetic differences between flavocytochromes b2 from the yeasts Hansenula anomala and Saccharomyces cerevisiae.
[6]
PubMed ID2207080
JournalBiochemistry
Year1990
Volume29
Pages6393-400
AuthorsDubois J, Chapman SK, Mathews FS, Reid GA, Lederer F
TitleSubstitution of Tyr254 with Phe at the active site of flavocytochrome b2: consequences on catalysis of lactate dehydrogenation.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
Medline ID90230315
PubMed ID2329585
JournalJ Mol Biol
Year1990
Volume212
Pages837-63
AuthorsXia ZX, Mathews FS
TitleMolecular structure of flavocytochrome b2 at 2.4 A resolution.
Related PDB1fcb
Related Swiss-protP00175
[8]
PubMed ID1637299
JournalBiochem J
Year1992
Volume285
Pages187-92
AuthorsMiles CS, Rouviere-Fourmy N, Lederer F, Mathews FS, Reid GA, Black MT, Chapman SK
TitleTyr-143 facilitates interdomain electron transfer in flavocytochrome b2.
[9]
PubMed ID8395046
JournalProteins
Year1993
Volume16
Pages408-22
AuthorsTegoni M, White SA, Roussel A, Mathews FS, Cambillau C
TitleA hypothetical complex between crystalline flavocytochrome b2 and cytochrome c.
[10]
PubMed ID7821541
JournalBiochem Soc Trans
Year1994
Volume22
Pages282S
AuthorsDaff S, Manson FD, Reid GA, Chapman SK
TitleManipulation of the substrate specificity of flavocytochrome b2.
[11]
PubMed ID8292608
JournalBiochemistry
Year1994
Volume33
Pages798-806
AuthorsRouviere-Fourmy N, Capeillere-Blandin C, Lederer F
TitleRole of tyrosine 143 in lactate dehydrogenation by flavocytochrome b2. Primary kinetic isotope effect studies with a phenylalanine mutant.
[12]
PubMed ID8142887
JournalProtein Sci
Year1994
Volume3
Pages109-17
AuthorsBalme A, Lederer F
TitleOn the rate of proton exchange with solvent of the catalytic histidine in flavocytochrome b2 (yeast L-lactate dehydrogenase).
[13]
CommentsX-ray crystallography
PubMed ID8003966
JournalProtein Sci
Year1994
Volume3
Pages303-13
AuthorsTegoni M, Cambillau C
TitleThe 2.6-A refined structure of the Escherichia coli recombinant Saccharomyces cerevisiae flavocytochrome b2-sulfite complex.
Related PDB1ltd
[14]
CommentsX-ray crystallography
PubMed ID7632684
JournalBiochemistry
Year1995
Volume34
Pages9840-50
AuthorsTegoni M, Begotti S, Cambillau C
TitleX-ray structure of two complexes of the Y143F flavocytochrome b2 mutant crystallized in the presence of lactate or phenyl lactate.
Related PDB1lco,1ldc
[15]
PubMed ID8589072
JournalBiochimie
Year1995
Volume77
Pages621-30
AuthorsGaume B, Sharp RE, Manson FD, Chapman SK, Reid GA, Lederer F
TitleMutation to glutamine of histidine 373, the catalytic base of flavocytochrome b2 (L-lactate dehydrogenase).
[16]
PubMed ID7663348
JournalProtein Sci
Year1995
Volume4
Pages925-35
AuthorsGondry M, Diep Le KH, Manson FD, Chapman SK, Mathews FS, Reid GA, Lederer F
TitleOn the lack of coordination between protein folding and flavin insertion in Escherichia coli for flavocytochrome b2 mutant forms Y254L and D282N.
[17]
PubMed ID8687394
JournalBiochem J
Year1996
Volume316
Pages507-13
AuthorsSharp RE, Chapman SK, Reid GA
TitleModulation of flavocytochrome b2 intraprotein electron transfer via an interdomain hinge region.
[18]
PubMed ID8639579
JournalBiochemistry
Year1996
Volume35
Pages6345-50
AuthorsDaff S, Ingledew WJ, Reid GA, Chapman SK
TitleNew insights into the catalytic cycle of flavocytochrome b2.
[19]
PubMed ID8679620
JournalBiochemistry
Year1996
Volume35
Pages8587-94
AuthorsGondry M, Lederer F
TitleFunctional properties of the histidine-aspartate ion pair of flavocytochrome b2 (L-lactate dehydrogenase): substitution of Asp282 with asparagine.
[20]
PubMed ID8755502
JournalProc Natl Acad Sci U S A
Year1996
Volume93
Pages7496-501
AuthorsMattevi A, Vanoni MA, Todone F, Rizzi M, Teplyakov A, Coda A, Bolognesi M, Curti B
TitleCrystal structure of D-amino acid oxidase: a case of active site mirror-image convergent evolution with flavocytochrome b2.
[21]
PubMed ID9188712
JournalBiochemistry
Year1997
Volume36
Pages7126-35
AuthorsRouviere N, Mayer M, Tegoni M, Capeillere-Blandin C, Lederer F
TitleMolecular interpretation of inhibition by excess substrate in flavocytochrome b2: a study with wild-type and Y143F mutant enzymes.
[22]
PubMed ID9220981
JournalBiochemistry
Year1997
Volume36
Pages8932-46
AuthorsTegoni M, Gervais M, Desbois A
TitleResonance Raman study on the oxidized and anionic semiquinone forms of flavocytochrome b2 and L-lactate monooxygenase. Influence of the structure and environment of the isoalloxazine ring on the flavin function.
[23]
PubMed ID9639570
JournalBiochem J
Year1998
Volume333
Pages117-20
AuthorsSinclair R, Reid GA, Chapman SK
TitleRe-design of Saccharomyces cerevisiae flavocytochrome b2: introduction of L-mandelate dehydrogenase activity.
[24]
PubMed ID9521665
JournalBiochemistry
Year1998
Volume37
Pages3440-8
AuthorsMiles CS, Lederer F, Le KH
TitleProbing intramolecular electron transfer within flavocytochrome b2 with a monoclonal antibody.
[25]
CommentsX-ray crystallography
PubMed ID10727218
JournalBiochemistry
Year2000
Volume39
Pages3266-75
AuthorsMowat CG, Beaudoin I, Durley RC, Barton JD, Pike AD, Chen ZW, Reid GA, Chapman SK, Mathews FS, Lederer F
TitleKinetic and crystallographic studies on the active site Arg289Lys mutant of flavocytochrome b2 (yeast L-lactate dehydrogenase).
Related PDB1qcw
[26]
PubMed ID10931200
JournalEur J Biochem
Year2000
Volume267
Pages5156-67
AuthorsFleischmann G, Lederer F, Muller F, Bacher A, Ruterjans H
TitleFlavin-protein interactions in flavocytochrome b2 as studied by NMR after reconstitution of the enzyme with 13C- and 15N-labelled flavin.
[27]
PubMed ID11170421
JournalBiochemistry
Year2001
Volume40
Pages994-1001
AuthorsSobrado P, Daubner SC, Fitzpatrick PF
TitleProbing the relative timing of hydrogen abstraction steps in the flavocytochrome b2 reaction with primary and solvent deuterium isotope effects and mutant enzymes.
[28]
PubMed ID11559361
JournalEur J Biochem
Year2001
Volume268
Pages4918-27
AuthorsGondry M, Dubois J, Terrier M, Lederer F
TitleThe catalytic role of tyrosine 254 in flavocytochrome b2 (L-lactate dehydrogenase from baker's yeast). Comparison between the Y254F and Y254L mutant proteins.

comments
This Enzyme (Flavocytochrome b2, E.C. 1.1.2.3) is also called L-lactate dehydrogenase, but different from E.C. 1.1.1.27.
According to the literature [18], this enzyme catalyzes several steps, in which the dehydrogenation of Lactate and electron transfers from b2-heme to cytochrome c occur independently.

createdupdated
2004-07-162009-02-26


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 2010)
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)

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