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Protein

Hydroxymethylglutaryl-CoA synthase

Gene

mvaS

Organism
Enterococcus faecalis (Streptococcus faecalis)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoid compounds.2 Publications

Catalytic activityi

Acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA.2 Publications

Enzyme regulationi

Is sensitive to feedback substrate inhibition by acetoacetyl-CoA. Is inactivated by hymeglusin, which also blocks the growth of E.faecalis, indicating the critical role that the mevalonate pathway plays in isoprenoid biosynthesis.3 Publications

Kineticsi

  1. KM=350 µM for acetyl-CoA2 Publications
  2. KM=10 µM for acetoacetyl-CoA2 Publications
  3. KM=400 µM for acetyl-CoA2 Publications
  4. KM=0.5 µM for acetoacetyl-CoA2 Publications
  1. Vmax=10 µmol/min/mg enzyme2 Publications
  2. Vmax=5.3 µmol/min/mg enzyme2 Publications

pH dependencei

Optimum pH is about 9.8.1 Publication

Temperature dependencei

Optimum temperature is 37 degrees Celsius.1 Publication

Pathwayi: (R)-mevalonate biosynthesis

This protein is involved in step 2 of the subpathway that synthesizes (R)-mevalonate from acetyl-CoA.1 Publication
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. no protein annotated in this organism
  2. Hydroxymethylglutaryl-CoA synthase (mvaS)
  3. no protein annotated in this organism
This subpathway is part of the pathway (R)-mevalonate biosynthesis, which is itself part of Metabolic intermediate biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-mevalonate from acetyl-CoA, the pathway (R)-mevalonate biosynthesis and in Metabolic intermediate biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei29 – 291SubstrateBy similarity
Active sitei79 – 791Proton donor/acceptorBy similarity
Active sitei111 – 1111Acyl-thioester intermediate1 Publication
Binding sitei201 – 2011SubstrateBy similarity
Active sitei233 – 2331Proton donor/acceptorBy similarity
Binding sitei275 – 2751SubstrateBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Isoprene biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-18245.
BRENDAi2.3.3.10. 2095.
SABIO-RKQ9FD71.
UniPathwayiUPA00058; UER00102.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxymethylglutaryl-CoA synthase (EC:2.3.3.10)
Short name:
HMG-CoA synthase
Short name:
HMGCS
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
Gene namesi
Name:mvaS
OrganismiEnterococcus faecalis (Streptococcus faecalis)
Taxonomic identifieri1351 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesEnterococcaceaeEnterococcus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi110 – 1101A → G: 140-fold increase in the overall reaction rate, and 86-fold increase in catalytic efficiency. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 383383Hydroxymethylglutaryl-CoA synthasePRO_0000429271Add
BLAST

Interactioni

Subunit structurei

Homodimer.3 Publications

Protein-protein interaction databases

STRINGi226185.EF1363.

Structurei

Secondary structure

1
383
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 119Combined sources
Beta strandi14 – 185Combined sources
Helixi19 – 257Combined sources
Helixi32 – 354Combined sources
Beta strandi41 – 433Combined sources
Helixi51 – 6010Combined sources
Helixi65 – 706Combined sources
Beta strandi71 – 777Combined sources
Beta strandi82 – 865Combined sources
Helixi88 – 958Combined sources
Beta strandi103 – 1097Combined sources
Helixi110 – 1123Combined sources
Helixi113 – 12715Combined sources
Beta strandi132 – 14110Combined sources
Helixi150 – 1523Combined sources
Beta strandi154 – 16512Combined sources
Beta strandi167 – 1715Combined sources
Beta strandi176 – 1794Combined sources
Beta strandi184 – 1863Combined sources
Helixi198 – 22023Combined sources
Helixi224 – 2263Combined sources
Beta strandi228 – 2325Combined sources
Helixi237 – 24812Combined sources
Helixi253 – 26614Combined sources
Turni267 – 2693Combined sources
Helixi270 – 2723Combined sources
Helixi277 – 2793Combined sources
Helixi280 – 29112Combined sources
Beta strandi300 – 3078Combined sources
Turni308 – 3103Combined sources
Beta strandi311 – 3199Combined sources
Helixi323 – 3264Combined sources
Helixi329 – 3379Combined sources
Helixi344 – 3529Combined sources
Beta strandi371 – 3755Combined sources
Beta strandi378 – 3814Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1X9EX-ray2.40A/B1-383[»]
1YSLX-ray1.90A/B1-383[»]
2HDBX-ray2.20A/B1-383[»]
3V4NX-ray1.60A/B/C/D1-383[»]
3V4XX-ray1.95A/B/C/D1-383[»]
ProteinModelPortaliQ9FD71.
SMRiQ9FD71. Positions 1-383.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9FD71.

Family & Domainsi

Sequence similaritiesi

Belongs to the HMG-CoA synthase family.Curated

Phylogenomic databases

eggNOGiENOG4105F99. Bacteria.
COG3425. LUCA.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR011554. HMG_CoA_synthase_prok.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 2 hits.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 2 hits.
TIGRFAMsiTIGR01835. HMG-CoA-S_prok. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9FD71-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTIGIDKISF FVPPYYIDMT ALAEARNVDP GKFHIGIGQD QMAVNPISQD
60 70 80 90 100
IVTFAANAAE AILTKEDKEA IDMVIVGTES SIDESKAAAV VLHRLMGIQP
110 120 130 140 150
FARSFEIKEA CYGATAGLQL AKNHVALHPD KKVLVVAADI AKYGLNSGGE
160 170 180 190 200
PTQGAGAVAM LVASEPRILA LKEDNVMLTQ DIYDFWRPTG HPYPMVDGPL
210 220 230 240 250
SNETYIQSFA QVWDEHKKRT GLDFADYDAL AFHIPYTKMG KKALLAKISD
260 270 280 290 300
QTEAEQERIL ARYEESIIYS RRVGNLYTGS LYLGLISLLE NATTLTAGNQ
310 320 330 340 350
IGLFSYGSGA VAEFFTGELV AGYQNHLQKE THLALLDNRT ELSIAEYEAM
360 370 380
FAETLDTDID QTLEDELKYS ISAINNTVRS YRN
Length:383
Mass (Da):42,151
Last modified:March 1, 2001 - v1
Checksum:iC3BE0D765FF15E42
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF290092 Genomic DNA. Translation: AAG02438.1.
RefSeqiWP_002357756.1. NZ_LQAM01000009.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF290092 Genomic DNA. Translation: AAG02438.1.
RefSeqiWP_002357756.1. NZ_LQAM01000009.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1X9EX-ray2.40A/B1-383[»]
1YSLX-ray1.90A/B1-383[»]
2HDBX-ray2.20A/B1-383[»]
3V4NX-ray1.60A/B/C/D1-383[»]
3V4XX-ray1.95A/B/C/D1-383[»]
ProteinModelPortaliQ9FD71.
SMRiQ9FD71. Positions 1-383.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi226185.EF1363.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG4105F99. Bacteria.
COG3425. LUCA.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00102.
BioCyciMetaCyc:MONOMER-18245.
BRENDAi2.3.3.10. 2095.
SABIO-RKQ9FD71.

Miscellaneous databases

EvolutionaryTraceiQ9FD71.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR011554. HMG_CoA_synthase_prok.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 2 hits.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 2 hits.
TIGRFAMsiTIGR01835. HMG-CoA-S_prok. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. "Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in gram-positive cocci."
    Wilding E.I., Brown J.R., Bryant A.P., Chalker A.F., Holmes D.J., Ingraham K.A., Iordanescu S., So C.Y., Rosenberg M., Gwynn M.N.
    J. Bacteriol. 182:4319-4327(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PATHWAY.
  2. "Enterococcus faecalis 3-hydroxy-3-methylglutaryl coenzyme A synthase, an enzyme of isopentenyl diphosphate biosynthesis."
    Sutherlin A., Hedl M., Sanchez-Neri B., Burgner J.W. II, Stauffacher C.V., Rodwell V.W.
    J. Bacteriol. 184:4065-4070(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
  3. "Expression in Haloferax volcanii of 3-hydroxy-3-methylglutaryl coenzyme A synthase facilitates isolation and characterization of the active form of a key enzyme required for polyisoprenoid cell membrane biosynthesis in halophilic archaea."
    VanNice J.C., Skaff D.A., Wyckoff G.J., Miziorko H.M.
    J. Bacteriol. 195:3854-3862(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, ENZYME REGULATION.
  4. "X-ray crystal structures of HMG-CoA synthase from Enterococcus faecalis and a complex with its second substrate/inhibitor acetoacetyl-CoA."
    Steussy C.N., Vartia A.A., Burgner J.W., Sutherlin A., Rodwell V.W., Stauffacher C.V.
    Biochemistry 44:14256-14267(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF APOENZYME AND OF A COVALENT ACETOACETYL-ENZYME ADDUCT IN COMPLEX WITH COA, SUBUNIT, ENZYME REGULATION, ACTIVE SITE, REACTION MECHANISM.
  5. Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT GLY-110, MUTAGENESIS OF ALA-110.
  6. "Biochemical and structural basis for inhibition of Enterococcus faecalis hydroxymethylglutaryl-CoA synthase, mvaS, by hymeglusin."
    Skaff D.A., Ramyar K.X., McWhorter W.J., Barta M.L., Geisbrecht B.V., Miziorko H.M.
    Biochemistry 51:4713-4722(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH HYMEGLUSIN INHIBITOR VIA A COVALENT LINKAGE, ENZYME REGULATION.

Entry informationi

Entry nameiHMGCS_ENTFL
AccessioniPrimary (citable) accession number: Q9FD71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 11, 2014
Last sequence update: March 1, 2001
Last modified: July 6, 2016
This is version 65 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.