ID HMGCS_HALVD Reviewed; 445 AA.
AC D4GWR6;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 27-MAR-2024, entry version 71.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase;
DE Short=HMG-CoA synthase;
DE Short=HMGCS;
DE EC=2.3.3.10;
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase;
GN Name=hmgB; OrderedLocusNames=HVO_2419; ORFNames=C498_07375;
OS Haloferax volcanii (strain ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 /
OS NCIMB 2012 / VKM B-1768 / DS2) (Halobacterium volcanii).
OC Archaea; Euryarchaeota; Stenosarchaea group; Halobacteria; Haloferacales;
OC Haloferacaceae; Haloferax.
OX NCBI_TaxID=309800;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 / VKM
RC B-1768 / DS2;
RX PubMed=20333302; DOI=10.1371/journal.pone.0009605;
RA Hartman A.L., Norais C., Badger J.H., Delmas S., Haldenby S., Madupu R.,
RA Robinson J., Khouri H., Ren Q., Lowe T.M., Maupin-Furlow J.,
RA Pohlschroder M., Daniels C., Pfeiffer F., Allers T., Eisen J.A.;
RT "The complete genome sequence of Haloferax volcanii DS2, a model
RT archaeon.";
RL PLoS ONE 5:E9605-E9605(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 / VKM
RC B-1768 / DS2;
RX PubMed=25393412; DOI=10.1371/journal.pgen.1004784;
RA Becker E.A., Seitzer P.M., Tritt A., Larsen D., Krusor M., Yao A.I., Wu D.,
RA Madern D., Eisen J.A., Darling A.E., Facciotti M.T.;
RT "Phylogenetically driven sequencing of extremely halophilic archaea reveals
RT strategies for static and dynamic osmo-response.";
RL PLoS Genet. 10:E1004784-E1004784(2014).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND PATHWAY.
RC STRAIN=DS2 / DS70;
RX PubMed=23794621; DOI=10.1128/jb.00485-13;
RA VanNice J.C., Skaff D.A., Wyckoff G.J., Miziorko H.M.;
RT "Expression in Haloferax volcanii of 3-hydroxy-3-methylglutaryl coenzyme A
RT synthase facilitates isolation and characterization of the active form of a
RT key enzyme required for polyisoprenoid cell membrane biosynthesis in
RT halophilic archaea.";
RL J. Bacteriol. 195:3854-3862(2013).
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 such as
CC archaeal membrane lipids. {ECO:0000269|PubMed:23794621}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-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 Evidence={ECO:0000269|PubMed:23794621};
CC -!- ACTIVITY REGULATION: In contrast to bacterial and eukaryotic HMG-CoA
CC synthases, is insensitive to feedback substrate inhibition by
CC acetoacetyl-CoA. Enzymatic activity is inhibited by hymeglusin, which
CC also blocks the propagation of H.volcanii cells in vivo, indicating the
CC critical role that the mevalonate pathway plays in isoprenoid
CC biosynthesis by these archaea. {ECO:0000269|PubMed:23794621}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for acetyl-CoA (at pH 8 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:23794621};
CC KM=1.4 uM for acetoacetyl-CoA (at pH 8 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:23794621};
CC Vmax=5.3 umol/min/mg enzyme (at pH 8 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:23794621};
CC Note=kcat is 4.6 sec(-1) (at pH 8 and 30 degrees Celsius).;
CC pH dependence:
CC Optimum pH is about 8.5. {ECO:0000269|PubMed:23794621};
CC Temperature dependence:
CC Optimum temperature is 45 degrees Celsius.
CC {ECO:0000269|PubMed:23794621};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC {ECO:0000269|PubMed:23794621}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
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DR EMBL; CP001956; ADE04128.1; -; Genomic_DNA.
DR EMBL; AOHU01000044; ELY32861.1; -; Genomic_DNA.
DR RefSeq; WP_004042308.1; NZ_AOHU01000044.1.
DR AlphaFoldDB; D4GWR6; -.
DR SMR; D4GWR6; -.
DR STRING; 309800.HVO_2419; -.
DR PaxDb; 309800-C498_07375; -.
DR EnsemblBacteria; ADE04128; ADE04128; HVO_2419.
DR GeneID; 8924297; -.
DR KEGG; hvo:HVO_2419; -.
DR PATRIC; fig|309800.29.peg.1430; -.
DR eggNOG; arCOG01767; Archaea.
DR HOGENOM; CLU_008065_3_2_2; -.
DR OrthoDB; 5812at2157; -.
DR BioCyc; MetaCyc:MONOMER-21128; -.
DR BRENDA; 2.3.3.10; 2561.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000008243; Chromosome.
DR Proteomes; UP000011532; Unassembled WGS sequence.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IEA:InterPro.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IEA:InterPro.
DR CDD; cd00827; init_cond_enzymes; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR013746; HMG_CoA_synt_C_dom.
DR InterPro; IPR013528; HMG_CoA_synth_N.
DR InterPro; IPR016039; Thiolase-like.
DR NCBIfam; NF041302; HMG_CoAsyn_Halo; 1.
DR PANTHER; PTHR43323; 3-HYDROXY-3-METHYLGLUTARYL COENZYME A SYNTHASE; 1.
DR PANTHER; PTHR43323:SF2; HYDROXYMETHYLGLUTARYL-COA SYNTHASE; 1.
DR Pfam; PF08540; HMG_CoA_synt_C; 1.
DR Pfam; PF01154; HMG_CoA_synt_N; 1.
DR SUPFAM; SSF53901; Thiolase-like; 2.
PE 1: Evidence at protein level;
KW Acyltransferase; Isoprene biosynthesis; Lipid biosynthesis;
KW Lipid metabolism; Reference proteome; Transferase.
FT CHAIN 1..445
FT /note="Hydroxymethylglutaryl-CoA synthase"
FT /id="PRO_0000429255"
FT ACT_SITE 83
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 120
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 244
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 31
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 211
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 328
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 445 AA; 50103 MW; F60D3572DBF2FF95 CRC64;
MTSVGIDAME IWTGKLVLDL PNTFAPVKGE DPEKYTKGLG LHTSSFPDVY EDIVTMGANA
AKKLMDRKGL TPADIGRIDV ATESAFDNSK PVSTYIAGCL EQVYDGDFRH ANKGERKFAC
IAGTQSLDDA YNWIKAGRNR GRAALVIATD TALYERGDPG EATQGAGAVA MLIDEDPDLV
ELSTEQGYGS MDETDFLKPN QQFPSVDGKR SMQVYLARMR EALEDYESVA GRTHPDLFEY
IPFHTPFPGM VRKAALLGFR HMTRDTDIED DLESEIGRQP REEDFETWDD YEEAIRGYMD
ELKTTEQYRD WYGRVIEPTL DISSRVGNWY TGSVHIARLS ALKAAADEGK DMTGKQLLVG
SYGSGAQAEI HAERVQETWL DEIEAVDVDD QLAARTEISF DDYELIHDVH NHEKEIEVEE
FTQPEAEFVF TGWGRMNERR YEYVE
//
