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hydroxymethylglutaryl-CoA synthase

Family: Lanosterol biosynthesis pathway

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Enzyme Reaction
Substrates and Reaction Kinetics
References
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 520 5p14-p13 HMGCS1 3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)
Mouse - 520 13 66.0 cM; 13 Hmgcs1 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1
Rat - 520 2q16 Hmgcs1 3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)
Previous and Unofficial Names
3-hydroxy-3-methylglutaryl coenzyme A synthase
3-hydroxy-3-methylglutaryl-CoA synthase
3-hydroxy-3-methylglutaryl-coenzyme A synthase
3-hydroxyl-3-methyl-glutaryl-CoA synthase
HMG-CoA
HMG-CoA synthase
(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating)
3-hydroxy-3-methylglutaryl CoA synthetase
3-hydroxy-3-methylglutaryl coenzyme A synthetase
acetoacetyl coenzyme A transacetase
beta-hydroxy-beta-methylglutaryl-CoA synthase
hydroxymethylglutaryl CoA synthetase
hydroxymethylglutaryl coenzyme A synthase
hydroxymethylglutaryl coenzyme A-condensing enzyme
hydroxymethylglutaryl-coenzyme A synthase
HMGCS
3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble)
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase
3-hydroxy-3-methylglutaryl-CoA synthase 1 (soluble)
3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1
hydroxymethylglutaryl-CoA synthase 1
hydroxymethylglutaryl-CoA synthase, cytoplasmic
Database Links
BRENDA 2.3.3.10
ChEMBL Target CHEMBL2189 (Rn)
Ensembl ENSG00000112972 (Hs), ENSMUSG00000079301 (Mm), ENSMUSG00000079828 (Mm), ENSRNOG00000016552 (Rn)
Entrez Gene 3157 (Hs), 208715 (Mm), 29637 (Rn)
ExplorEnz 2.3.3.10
GeneCards HMGCS1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Hmgcs1 (Mm)
Human Protein Reference Database 07515 (Hs)
InterPro Q01581 (Hs), Q8JZK9 (Mm), P17425 (Rn)
KEGG BRITE Hierarchy 2.3.3.10
KEGG Gene hsa:3157 (Hs), mmu:208715 (Mm), rno:29637 (Rn)
OMIM 142940 (Hs)
PharmGKB Gene PA29337 (Hs)
PhosphoSitePlus Q01581 (Hs), Q8JZK9 (Mm), P17425 (Rn)
RefSeq Nucleotide NM_002130 (Hs), NM_001098272 (Hs), NM_145942 (Mm), NM_017268 (Rn)
RefSeq Protein NP_002121 (Hs), NP_001091742 (Hs), NP_666054 (Mm), NP_058964 (Rn)
TreeFam ENSG00000112972 (Hs), ENSMUSG00000079301 (Mm), ENSMUSG00000079828 (Mm), ENSRNOG00000016552 (Rn)
UniGene Hs. 397729 (Hs)
UniProt Q01581 (Hs), Q8JZK9 (Mm), P17425 (Rn)
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human 3-hydroxy-3-methylglutaryl CoA synthase I
PDB Id:  2P8U
Resolution:  2.0Å
Species:  Human
References:  3
Search for other structures on the PDB
Search by keyword: Lanosterol biosynthesis pathway hydroxymethylglutaryl-CoA synthase Search by accession number: Q01581, Q8JZK9, P17425
Enzyme Reaction
EC Number: 2.3.3.10 acetyl CoA + H2O + acetoacetyl CoA -> (S)-3-hydroxy-3-methylglutaryl-CoA + coenzyme A
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Assay description Assay conditions Comments Reference
acetyl CoA Hs Km 29.0 µM pH 8.2, 30ºC 2
acetyl CoA Hs Km 73.0 µM Recombinant human HMG CoA synthase was produced in Escherichia coli, microplate analysis for purified enzyme. In vitro. pH 8.2, 30ºC 1
acetyl CoA Hs Km 76.0 µM Recombinant human HMG CoA synthase was produced in Escherichia coli, microplate analysis for purified enzyme. In vitro. pH 8.0, 30ºC ΔA412 nm assay (DTNB measurement of coenzyme A formation) 1
acetyl CoA Hs Km 84.0 µM Recombinant human HMG CoA synthase was produced in Escherichia coli, microplate analysis for purified enzyme. In vitro. pH 8.0, 30ºC ΔA300 nm assay (acetoacetyl-CoA use) 1
acetoacetyl CoA Hs Km 5.0 µM Recombinant human HMG CoA synthase was produced in Escherichia coli, microplate analysis for purified enzyme. In vitro. pH 8.0, 30ºC ΔA412 nm assay (microplate format). Recorded as 5 +/- 1 1
acetyl CoA Hs Vmax 0.67 µmol/min/mg Recombinant human HMG CoA synthase was produced in Escherichia coli, microplate analysis for purified enzyme. In vitro. pH 8.0, 30ºC ΔA412 nm assay (microplate format) 1
acetyl CoA Hs Vmax 1.04 µmol/min/mg Recombinant human HMG CoA synthase was produced in Escherichia coli, microplate analysis for purified enzyme. In vitro. pH 8.0, 30ºC ΔA412 nm assay (DTNB measurement of coenzyme A formation). Recorded as 1.04 ± 0.03. 1
acetyl CoA Hs Vmax 1.06 µmol/min/mg Recombinant human HMG CoA synthase was produced in Escherichia coli, microplate analysis for purified enzyme. In vitro. pH 8.0, 30ºC sulfhydryl detection using DTNB measured at wavelength 420 nm. Recorded as 1.06 ± 0.04 1

REFERENCES

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1. Andrew Skaff, D; Miziorko, HM. (2010) A visible wavelength spectrophotometric assay suitable for high-throughput screening of 3-hydroxy-3-methylglutaryl-CoA synthase. Anal. Biochem., 396 (1): 96-102. [PMID:19706283]

2. Rokosz, LL; Boulton, DA; Butkiewicz, EA; Sanyal, G; Cueto, MA; Lachance, PA; Hermes, JD. (1994) Human cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase: expression, purification, and characterization of recombinant wild-type and Cys129 mutant enzymes. Arch. Biochem. Biophys., 312 (1): 1-13. [PMID:7913309]

3. Shafqat, N; Turnbull, A; Zschocke, J; Oppermann, U; Yue, WW. (2010) Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. J. Mol. Biol., 398 (4): 497-506. [PMID:20346956]

To cite this database page, please use the following:

Helen E. Benson.
Lanosterol biosynthesis pathway: hydroxymethylglutaryl-CoA synthase. Last modified on 09/02/2012. Accessed on 22/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=63804.


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