AC   MF_01409;
DC   Protein; auto
TR   HAMAP; MF_01409; -; 1; level=0
XX
Names: HMG-CoA_synth_arch
XX
ID   HMGCS
DE   RecName: Full=Hydroxymethylglutaryl-CoA synthase;
DE            Short=HMG-CoA synthase;
DE            Short=HMGCS;
DE            EC=2.3.3.10;
XX
CC   -!- FUNCTION: Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA
CC       to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Functions in the
CC       mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a
CC       key precursor for the biosynthesis of isoprenoid compounds that are
CC       building blocks of archaeal membrane lipids.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-3-hydroxy-3-
CC         methylglutaryl-CoA + CoA + H(+); Xref=Rhea:RHEA:10188,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43074,
CC         ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.10;
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC   -!- SUBUNIT: Interacts with acetoacetyl-CoA thiolase that catalyzes the
CC       precedent step in the pathway and with a DUF35 protein. The
CC       acetoacetyl-CoA thiolase/HMG-CoA synthase complex channels the
CC       intermediate via a fused CoA-binding site, which allows for efficient
CC       coupling of the endergonic thiolase reaction with the exergonic HMGCS
CC       reaction.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. Archaeal HMG-CoA
CC       synthase family.
XX
DR   Pfam; PF01154; HMG_CoA_synt_N; 1; trigger=no
DR   Pfam; PF08541; ACP_syn_III_C; 1; trigger=no
DR   NCBIfam; TIGR00748; HMG_CoA_syn_Arc; 1; trigger=no
XX
KW   Acyltransferase
KW   Isoprene biosynthesis
KW   Transferase
XX
GO   GO:0003985; F:acetyl-CoA C-acetyltransferase activity
GO   GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway
XX
FT   From: HMGCS_METAR (Q0W7K1)
FT   ACT_SITE        80
FT                   /note="Proton donor/acceptor"
FT   Condition: E
FT   ACT_SITE        112
FT                   /note="Acyl-thioester intermediate"
FT   Condition: C
FT   ACT_SITE        234
FT                   /note="Proton donor/acceptor"
FT   Condition: H
FT   BINDING         29
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Optional; Condition: [DE]
FT   BINDING         30
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Optional; Condition: [AV]
FT   BINDING         112
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Condition: C
FT   BINDING         153
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Condition: [TS]
FT   BINDING         199
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /ligand_note="ligand shared with acetoacetyl-CoA thiolase"
FT   Optional; Condition: [RK]
FT   BINDING         201
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Condition: [TS]
FT   BINDING         234
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Condition: H
FT   BINDING         239
FT                   /ligand="CoA"
FT                   /ligand_id="ChEBI:CHEBI:57287"
FT                   /ligand_note="ligand shared with acetoacetyl-CoA thiolase"
FT   Condition: [KR]
FT   BINDING         243
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Optional; Condition: [RK]
FT   BINDING         266
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Condition: N
FT   BINDING         296
FT                   /ligand="(3S)-hydroxy-3-methylglutaryl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:43074"
FT   Condition: S
XX
Size: 343-365;
Related: None;
Template: A0A384E143;
Scope:
 Archaea
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Version: 20
# Last updated date: 2024-10-31
# Created date: 2005-02-28
//