DB code: D00014

CATH domain 3.10.120.10 : Flavocytochrome B2; Chain A, domain 1
3.20.20.70 : TIM Barrel Catalytic domain
E.C. 1.1.2.3
CSA 1fcb
M-CSA 1fcb
MACiE M0102

CATH domain Related DB codes (homologues)
3.10.120.10 : Flavocytochrome B2; Chain A, domain 1 T00018
3.20.20.70 : TIM Barrel S00215 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P00175 Cytochrome b2, mitochondrial
EC 1.1.2.3
L-lactate dehydrogenase [Cytochrome]
L-lactate ferricytochrome C oxidoreductase
L-LCR
NP_013658.1 (Protein)
NM_001182412.1 (DNA/RNA sequence)
PF00173 (Cyt-b5)
PF01070 (FMN_dh)
[Graphical View]

KEGG enzyme name
L-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P00175 CYB2_YEAST (S)-lactate + 2 ferricytochrome c = pyruvate + 2 ferrocytochrome c + 2 H(+). Homotetramer. Mitochondrion intermembrane space. FMN. Protoheme IX groups.

KEGG Pathways
Map code Pathways E.C.
MAP00620 Pyruvate metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00061 C00032 C00186 C00125 C00022 C00126
E.C.
Compound FMN Protoheme (S)-Lactate Ferricytochrome c Pyruvate Ferrocytochrome c
Type amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ion aromatic ring (with nitrogen atoms),carboxyl group,heavy metal carbohydrate,carboxyl group amide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide group carbohydrate,carboxyl group amide group,amine group,aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,sulfide group
ChEBI 17621
 17621
 		17627
 26355
 17627
 26355
 		422
 422
 		32816
 32816
PubChem 643976
 643976
 		107689
 107689
 		1060
 1060
1fcbA01 Unbound Bound:HEM Unbound Unbound Unbound Unbound
1lcoA01 Unbound Bound:HEM Unbound Unbound Unbound Unbound
1ldcA01 Unbound Bound:HEM Unbound Unbound Unbound Unbound
1ltdA01 Unbound Bound:HEM Unbound Unbound Unbound Unbound
1fcbA02 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1fcbB Bound:FMN Unbound Unbound Unbound Analogue:PYR Unbound
1lcoA02 Bound:FMN Unbound Unbound Unbound Analogue:PPY Unbound
1lcoB Bound:FMN Unbound Unbound Unbound Analogue:PPY Unbound
1ldcA02 Bound:FMN Unbound Unbound Unbound Analogue:PYR Unbound
1ldcB Bound:FMN Unbound Unbound Unbound Analogue:PYR Unbound
1ltdA02 Bound:FMN Unbound Unbound Unbound Unbound Unbound
1ltdB Analogue:FMN-SO3 Unbound Unbound Unbound Unbound Unbound
1qcwA01 Analogue:FNS Unbound Unbound Unbound Unbound Unbound
1qcwB01 Analogue:FNS Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P00175 & literature [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
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)
1fcbA02 TYR 254;ASP 282;HIS 373;ARG 376
1fcbB TYR 254;ASP 282;HIS 373;ARG 376
1lcoA02 TYR 254;ASP 282;HIS 373;ARG 376 mutant Y143F
1lcoB TYR 254;ASP 282;HIS 373;ARG 376 mutant Y143F
1ldcA02 TYR 254;ASP 282;HIS 373;ARG 376 mutant Y143F
1ldcB TYR 254;ASP 282;HIS 373;ARG 376 mutant Y143F
1ltdA02 TYR 254;ASP 282;HIS 373;ARG 376
1ltdB TYR 254;ASP 282;HIS 373;ARG 376
1qcwA01 TYR 254;ASP 282;HIS 373;ARG 376 mutant R289K;P304F,invisible F304
1qcwB01 TYR 254;ASP 282;HIS 373;ARG 376 mutant R289K;P304F,invisible F304

References for Catalytic Mechanism
References Sections No. 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.1 2
[18]
p.6347-6349, Fig.1
[19]
Fig.1, p.8593
[26]
p.5165-5166
[27]
Scheme 2 3
[28]
Fig.1 p.4925-4926

References
[1]
Resource
Comments
Medline ID
PubMed ID 6386468
Journal Eur J Biochem
Year 1984
Volume 144
Pages 345-51
Authors Urban P, Lederer F
Title Baker's yeast flavocytochrome b2. A mechanistic study of the dehydrohalogenation reaction.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3554243
Journal Proc Natl Acad Sci U S A
Year 1987
Volume 84
Pages 2629-33
Authors Xia ZX, Shamala N, Bethge PH, Lim LW, Bellamy HD, Xuong NH, Lederer F, Mathews FS
Title Three-dimensional structure of flavocytochrome b2 from baker's yeast at 3.0-A resolution.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3061453
Journal Biochemistry
Year 1988
Volume 27
Pages 7365-71
Authors Urban P, Chirat I, Lederer F
Title Rat kidney L-2-hydroxyacid oxidase. Structural and mechanistic comparison with flavocytochrome b2 from baker's yeast.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3058697
Journal J Biol Chem
Year 1988
Volume 263
Pages 19278-81
Authors Tegoni M, Mathews FS
Title Crystallographic study of the complex between sulfite and bakers' yeast flavocytochrome b2.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2688640
Journal Biochem J
Year 1989
Volume 263
Pages 973-6
Authors Black MT, Gunn FJ, Chapman SK, Reid GA
Title Structural basis for the kinetic differences between flavocytochromes b2 from the yeasts Hansenula anomala and Saccharomyces cerevisiae.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 2207080
Journal Biochemistry
Year 1990
Volume 29
Pages 6393-400
Authors Dubois J, Chapman SK, Mathews FS, Reid GA, Lederer F
Title Substitution of Tyr254 with Phe at the active site of flavocytochrome b2: consequences on catalysis of lactate dehydrogenation.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS)
Medline ID 90230315
PubMed ID 2329585
Journal J Mol Biol
Year 1990
Volume 212
Pages 837-63
Authors Xia ZX, Mathews FS
Title Molecular structure of flavocytochrome b2 at 2.4 A resolution.
Related PDB 1fcb
Related UniProtKB P00175
[8]
Resource
Comments
Medline ID
PubMed ID 1637299
Journal Biochem J
Year 1992
Volume 285
Pages 187-92
Authors Miles CS, Rouviere-Fourmy N, Lederer F, Mathews FS, Reid GA, Black MT, Chapman SK
Title Tyr-143 facilitates interdomain electron transfer in flavocytochrome b2.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8395046
Journal Proteins
Year 1993
Volume 16
Pages 408-22
Authors Tegoni M, White SA, Roussel A, Mathews FS, Cambillau C
Title A hypothetical complex between crystalline flavocytochrome b2 and cytochrome c.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7821541
Journal Biochem Soc Trans
Year 1994
Volume 22
Pages 282S
Authors Daff S, Manson FD, Reid GA, Chapman SK
Title Manipulation of the substrate specificity of flavocytochrome b2.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8292608
Journal Biochemistry
Year 1994
Volume 33
Pages 798-806
Authors Rouviere-Fourmy N, Capeillere-Blandin C, Lederer F
Title Role of tyrosine 143 in lactate dehydrogenation by flavocytochrome b2. Primary kinetic isotope effect studies with a phenylalanine mutant.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8142887
Journal Protein Sci
Year 1994
Volume 3
Pages 109-17
Authors Balme A, Lederer F
Title On the rate of proton exchange with solvent of the catalytic histidine in flavocytochrome b2 (yeast L-lactate dehydrogenase).
Related PDB
Related UniProtKB
[13]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 8003966
Journal Protein Sci
Year 1994
Volume 3
Pages 303-13
Authors Tegoni M, Cambillau C
Title The 2.6-A refined structure of the Escherichia coli recombinant Saccharomyces cerevisiae flavocytochrome b2-sulfite complex.
Related PDB 1ltd
Related UniProtKB
[14]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 7632684
Journal Biochemistry
Year 1995
Volume 34
Pages 9840-50
Authors Tegoni M, Begotti S, Cambillau C
Title X-ray structure of two complexes of the Y143F flavocytochrome b2 mutant crystallized in the presence of lactate or phenyl lactate.
Related PDB 1lco 1ldc
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8589072
Journal Biochimie
Year 1995
Volume 77
Pages 621-30
Authors Gaume B, Sharp RE, Manson FD, Chapman SK, Reid GA, Lederer F
Title Mutation to glutamine of histidine 373, the catalytic base of flavocytochrome b2 (L-lactate dehydrogenase).
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 7663348
Journal Protein Sci
Year 1995
Volume 4
Pages 925-35
Authors Gondry M, Diep Le KH, Manson FD, Chapman SK, Mathews FS, Reid GA, Lederer F
Title On the lack of coordination between protein folding and flavin insertion in Escherichia coli for flavocytochrome b2 mutant forms Y254L and D282N.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 8687394
Journal Biochem J
Year 1996
Volume 316
Pages 507-13
Authors Sharp RE, Chapman SK, Reid GA
Title Modulation of flavocytochrome b2 intraprotein electron transfer via an interdomain hinge region.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 8639579
Journal Biochemistry
Year 1996
Volume 35
Pages 6345-50
Authors Daff S, Ingledew WJ, Reid GA, Chapman SK
Title New insights into the catalytic cycle of flavocytochrome b2.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 8679620
Journal Biochemistry
Year 1996
Volume 35
Pages 8587-94
Authors Gondry M, Lederer F
Title Functional properties of the histidine-aspartate ion pair of flavocytochrome b2 (L-lactate dehydrogenase): substitution of Asp282 with asparagine.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 8755502
Journal Proc Natl Acad Sci U S A
Year 1996
Volume 93
Pages 7496-501
Authors Mattevi A, Vanoni MA, Todone F, Rizzi M, Teplyakov A, Coda A, Bolognesi M, Curti B
Title Crystal structure of D-amino acid oxidase: a case of active site mirror-image convergent evolution with flavocytochrome b2.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9188712
Journal Biochemistry
Year 1997
Volume 36
Pages 7126-35
Authors Rouviere N, Mayer M, Tegoni M, Capeillere-Blandin C, Lederer F
Title Molecular interpretation of inhibition by excess substrate in flavocytochrome b2: a study with wild-type and Y143F mutant enzymes.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 9220981
Journal Biochemistry
Year 1997
Volume 36
Pages 8932-46
Authors Tegoni M, Gervais M, Desbois A
Title Resonance 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.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 9639570
Journal Biochem J
Year 1998
Volume 333
Pages 117-20
Authors Sinclair R, Reid GA, Chapman SK
Title Re-design of Saccharomyces cerevisiae flavocytochrome b2: introduction of L-mandelate dehydrogenase activity.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 9521665
Journal Biochemistry
Year 1998
Volume 37
Pages 3440-8
Authors Miles CS, Lederer F, Le KH
Title Probing intramolecular electron transfer within flavocytochrome b2 with a monoclonal antibody.
Related PDB
Related UniProtKB
[25]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10727218
Journal Biochemistry
Year 2000
Volume 39
Pages 3266-75
Authors Mowat CG, Beaudoin I, Durley RC, Barton JD, Pike AD, Chen ZW, Reid GA, Chapman SK, Mathews FS, Lederer F
Title Kinetic and crystallographic studies on the active site Arg289Lys mutant of flavocytochrome b2 (yeast L-lactate dehydrogenase).
Related PDB 1qcw
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10931200
Journal Eur J Biochem
Year 2000
Volume 267
Pages 5156-67
Authors Fleischmann G, Lederer F, Muller F, Bacher A, Ruterjans H
Title Flavin-protein interactions in flavocytochrome b2 as studied by NMR after reconstitution of the enzyme with 13C- and 15N-labelled flavin.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 11170421
Journal Biochemistry
Year 2001
Volume 40
Pages 994-1001
Authors Sobrado P, Daubner SC, Fitzpatrick PF
Title Probing the relative timing of hydrogen abstraction steps in the flavocytochrome b2 reaction with primary and solvent deuterium isotope effects and mutant enzymes.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11559361
Journal Eur J Biochem
Year 2001
Volume 268
Pages 4918-27
Authors Gondry M, Dubois J, Terrier M, Lederer F
Title The catalytic role of tyrosine 254 in flavocytochrome b2 (L-lactate dehydrogenase from baker's yeast). Comparison between the Y254F and Y254L mutant proteins.
Related PDB
Related UniProtKB

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.

Created Updated
2004-07-16 2009-02-26