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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)DescriptionActionsGraphical viewLength
Binding sitei29SubstrateBy similarity1
Active sitei79Proton donor/acceptorBy similarity1
Active sitei111Acyl-thioester intermediate1 Publication1
Binding sitei201SubstrateBy similarity1
Active sitei233Proton donor/acceptorBy similarity1
Binding sitei275SubstrateBy similarity1

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)DescriptionActionsGraphical viewLength
Mutagenesisi110A → G: 140-fold increase in the overall reaction rate, and 86-fold increase in catalytic efficiency. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004292711 – 383Hydroxymethylglutaryl-CoA synthaseAdd BLAST383

Interactioni

Subunit structurei

Homodimer.3 Publications

Protein-protein interaction databases

STRINGi226185.EF1363.

Structurei

Secondary structure

1383
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 11Combined sources9
Beta strandi14 – 18Combined sources5
Helixi19 – 25Combined sources7
Helixi32 – 35Combined sources4
Beta strandi41 – 43Combined sources3
Helixi51 – 60Combined sources10
Helixi65 – 70Combined sources6
Beta strandi71 – 77Combined sources7
Beta strandi82 – 86Combined sources5
Helixi88 – 95Combined sources8
Beta strandi103 – 109Combined sources7
Helixi110 – 112Combined sources3
Helixi113 – 127Combined sources15
Beta strandi132 – 141Combined sources10
Helixi150 – 152Combined sources3
Beta strandi154 – 165Combined sources12
Beta strandi167 – 171Combined sources5
Beta strandi176 – 179Combined sources4
Beta strandi184 – 186Combined sources3
Helixi198 – 220Combined sources23
Helixi224 – 226Combined sources3
Beta strandi228 – 232Combined sources5
Helixi237 – 248Combined sources12
Helixi253 – 266Combined sources14
Turni267 – 269Combined sources3
Helixi270 – 272Combined sources3
Helixi277 – 279Combined sources3
Helixi280 – 291Combined sources12
Beta strandi300 – 307Combined sources8
Turni308 – 310Combined sources3
Beta strandi311 – 319Combined sources9
Helixi323 – 326Combined sources4
Helixi329 – 337Combined sources9
Helixi344 – 352Combined sources9
Beta strandi371 – 375Combined sources5
Beta strandi378 – 381Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
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_MBRC01000189.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF290092 Genomic DNA. Translation: AAG02438.1.
RefSeqiWP_002357756.1. NZ_MBRC01000189.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
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...

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: November 2, 2016
This is version 67 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.