LDHA_SQUAC
ID LDHA_SQUAC Reviewed; 333 AA.
AC P00341; Q92114;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=L-lactate dehydrogenase A chain;
DE Short=LDH-A;
DE EC=1.1.1.27 {ECO:0000250|UniProtKB:P00338};
DE AltName: Full=LDH-M;
GN Name=ldha;
OS Squalus acanthias (Spiny dogfish).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Chondrichthyes;
OC Elasmobranchii; Squalomorphii; Squaliformes; Squalidae; Squalus.
OX NCBI_TaxID=7797;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=8541980;
RA Stock D.W., Powers D.A.;
RT "The cDNA sequence of the lactate dehydrogenase-A of the spiny dogfish
RT (Squalus acanthias): corrections to the amino acid sequence and an analysis
RT of the phylogeny of vertebrate lactate dehydrogenases.";
RL Mol. Mar. Biol. Biotechnol. 4:284-294(1995).
RN [2]
RP PROTEIN SEQUENCE OF 2-333, AND ACETYLATION AT ALA-2.
RX PubMed=838743; DOI=10.1016/s0021-9258(17)40621-1;
RA Taylor S.S.;
RT "Amino acid sequence of dogfish muscle lactate dehydrogenase.";
RL J. Biol. Chem. 252:1799-1806(1977).
RN [3]
RP X-RAY CRYSTALLOGRAPHY.
RX PubMed=4795361; DOI=10.1016/0006-291x(73)91398-3;
RA Adams M.J., Ford G.C., Liljas A., Rossmann M.G.;
RT "Atomic co-ordinates for dogfish M4 apo-lactate dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 53:46-51(1973).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=197516; DOI=10.1073/pnas.74.7.2677;
RA Eventoff W., Rossmann M.G., Taylor S.S., Torff H.-J., Meyer H., Keil W.,
RA Kiltz H.-H.;
RT "Structural adaptations of lactate dehydrogenase isozymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 74:2677-2681(1977).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH NAD AND SUBSTRATE
RP ANALOG.
RX PubMed=3430615; DOI=10.1016/0022-2836(87)90293-2;
RA Abad-Zapatero C., Griffith J.P., Sussman J.L., Rossmann M.G.;
RT "Refined crystal structure of dogfish M4 apo-lactate dehydrogenase.";
RL J. Mol. Biol. 198:445-467(1987).
CC -!- FUNCTION: Interconverts simultaneously and stereospecifically pyruvate
CC and lactate with concomitant interconversion of NADH and NAD(+).
CC {ECO:0000250|UniProtKB:P00338}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate;
CC Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27;
CC Evidence={ECO:0000250|UniProtKB:P00338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23445;
CC Evidence={ECO:0000250|UniProtKB:P00338};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23446;
CC Evidence={ECO:0000250|UniProtKB:P00338};
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate
CC from pyruvate: step 1/1. {ECO:0000250|UniProtKB:P00338}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:3430615}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.
CC {ECO:0000305}.
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DR EMBL; U38893; AAA91038.1; -; mRNA.
DR PIR; A00350; DEDFLM.
DR PDB; 1LDM; X-ray; 2.10 A; A=2-333.
DR PDB; 3LDH; X-ray; 3.00 A; A=4-333.
DR PDB; 6LDH; X-ray; 2.00 A; A=2-333.
DR PDB; 8LDH; X-ray; 2.80 A; A=2-333.
DR PDBsum; 1LDM; -.
DR PDBsum; 3LDH; -.
DR PDBsum; 6LDH; -.
DR PDBsum; 8LDH; -.
DR AlphaFoldDB; P00341; -.
DR SMR; P00341; -.
DR iPTMnet; P00341; -.
DR SABIO-RK; P00341; -.
DR UniPathway; UPA00554; UER00611.
DR EvolutionaryTrace; P00341; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0019752; P:carboxylic acid metabolic process; IEA:InterPro.
DR Gene3D; 3.90.110.10; -; 1.
DR HAMAP; MF_00488; Lactate_dehydrog; 1.
DR InterPro; IPR001557; L-lactate/malate_DH.
DR InterPro; IPR011304; L-lactate_DH.
DR InterPro; IPR018177; L-lactate_DH_AS.
DR InterPro; IPR022383; Lactate/malate_DH_C.
DR InterPro; IPR001236; Lactate/malate_DH_N.
DR InterPro; IPR015955; Lactate_DH/Glyco_Ohase_4_C.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR PRINTS; PR00086; LLDHDRGNASE.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01771; L-LDH-NAD; 1.
DR PROSITE; PS00064; L_LDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; NAD;
KW Oxidoreductase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:838743"
FT CHAIN 2..333
FT /note="L-lactate dehydrogenase A chain"
FT /id="PRO_0000168455"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT BINDING 30..58
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:3430615"
FT BINDING 100
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:3430615"
FT BINDING 107
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 139
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 139
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 170
FT /ligand="substrate"
FT BINDING 249
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:838743"
FT CONFLICT 124
FT /note="D -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="S -> C (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 198..200
FT /note="SVP -> VPS (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 206..211
FT /note="NVAGVS -> WNA (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="D -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 226..227
FT /note="EN -> QD (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 286..287
FT /note="ND -> DN (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 297..298
FT /note="DN -> ND (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 4..8
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 21..27
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 31..41
FT /evidence="ECO:0007829|PDB:6LDH"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 56..68
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 84..87
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 107..128
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:1LDM"
FT HELIX 141..152
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 165..179
FT /evidence="ECO:0007829|PDB:6LDH"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:3LDH"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 223..228
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 230..246
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 251..265
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 289..297
FT /evidence="ECO:0007829|PDB:6LDH"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:6LDH"
FT HELIX 311..327
FT /evidence="ECO:0007829|PDB:6LDH"
SQ SEQUENCE 333 AA; 36695 MW; 20C3B5F84B6C0117 CRC64;
MATLKDKLIG HLATSQEPRS YNKITVVGVG AVGMACAISI LMKDLADEVA LVDVMEDKLK
GEMMDLQHGS LFLHTAKIVS GKDYSVSAGS KLVVITAGAR QQEGESRLNL VQRNVNIFKF
IIPDIVKHSP DCIILVVSNP VDVLTYVAWK LSGLPMHRII GSGCNLDSAR FRYLMGERLG
VHSSSCHGWV IGEHGDSSVP VWSGMNVAGV SLKELHPELG TDKDKENWKK LHKDVVDSAY
EVIKLKGYTS WAIGLSVADL AETIMKNLCR VHPVSTMVKD FYGIKNDVFL SLPCVLDNHG
ISNIVKMKLK PDEEQQLQKS ATTLWDIQKD LKF
