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Lyase PDB id
Protein chains
387 a.a. *
CAA ×4
Waters ×374
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Staphylococcus aureus 3-hydroxy-3-methylglutaryl-coa synthase
Structure: 3-hydroxy-3-methylglutaryl-coa synthase. Chain: a, b, c, d. Synonym: hmg-coa synthase. Engineered: yes. Other_details: complexed with acetoacetyl-coa
Source: Staphylococcus aureus. Organism_taxid: 1280. Gene: mvas. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.191     R-free:   0.255
Authors: N.Campobasso,M.Patel,I.E.Wilding,H.Kallender,M.Rosenberg, M.Gwynn
Key ref:
N.Campobasso et al. (2004). Staphylococcus aureus 3-hydroxy-3-methylglutaryl-CoA synthase: crystal structure and mechanism. J Biol Chem, 279, 44883-44888. PubMed id: 15292254 DOI: 10.1074/jbc.M407882200
06-Jul-04     Release date:   31-Aug-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9FD87  (Q9FD87_STAAU) -  HMG-CoA synthase
388 a.a.
387 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     2 terms  


DOI no: 10.1074/jbc.M407882200 J Biol Chem 279:44883-44888 (2004)
PubMed id: 15292254  
Staphylococcus aureus 3-hydroxy-3-methylglutaryl-CoA synthase: crystal structure and mechanism.
N.Campobasso, M.Patel, I.E.Wilding, H.Kallender, M.Rosenberg, M.N.Gwynn.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, a member of the family of acyl-condensing enzymes, catalyzes the first committed step in the mevalonate pathway and is a potential target for novel antibiotics and cholesterol-lowering agents. The Staphylococcus aureus mvaS gene product (43.2 kDa) was overexpressed in Escherichia coli, purified to homogeneity, and shown biochemically to be an HMG-CoA synthase. The crystal structure of the full-length enzyme was determined at 2.0-A resolution, representing the first structure of an HMG-CoA synthase from any organism. HMG-CoA synthase forms a homodimer. The monomer, however, contains an important core structure of two similar alpha/beta motifs, a fold that is completely conserved among acyl-condensing enzymes. This common fold provides a scaffold for a catalytic triad made up of Cys, His, and Asn required by these enzymes. In addition, a crystal structure of HMG-CoA synthase with acetoacetyl-CoA was determined at 2.5-A resolution. Together, these structures provide the structural basis for an understanding of the mechanism of HMG-CoA synthase.
  Selected figure(s)  
Figure 2.
FIG. 2. The overall architecture of HMG-CoA synthase. a, ribbon drawing of the HMG-CoA synthase monomer structure with strands and helices. -strands are green; -helices are cyan. The lower region is colored orange to distinguish it from the upper region, as discussed under "Results and Discussion." b, HMG-CoA synthase dimer with acetoacetyl-CoA depicted as a ball-and-stick model with 2F[o] - F[c] electron density of acetoacetyl-CoA.
Figure 4.
FIG. 4. View of the active site residues (a) and schematic representation of proposed mechanism (b).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 44883-44888) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19221601 H.Tsuruta, C.J.Paddon, D.Eng, J.R.Lenihan, T.Horning, L.C.Anthony, R.Regentin, J.D.Keasling, N.S.Renninger, and J.D.Newman (2009).
High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli.
  PLoS ONE, 4, e4489.  
16356722 A.M.Haapalainen, G.Meriläinen, and R.K.Wierenga (2006).
The thiolase superfamily: condensing enzymes with diverse reaction specificities.
  Trends Biochem Sci, 31, 64-71.  
16864776 F.Pojer, J.L.Ferrer, S.B.Richard, D.A.Nagegowda, M.L.Chye, T.J.Bach, and J.P.Noel (2006).
Structural basis for the design of potent and species-specific inhibitors of 3-hydroxy-3-methylglutaryl CoA synthases.
  Proc Natl Acad Sci U S A, 103, 11491-11496.
PDB codes: 2f82 2f9a 2fa0 2fa3
16835859 V.Simunovic, J.Zapp, S.Rachid, D.Krug, P.Meiser, and R.Müller (2006).
Myxovirescin A biosynthesis is directed by hybrid polyketide synthases/nonribosomal peptide synthetase, 3-hydroxy-3-methylglutaryl-CoA synthases, and trans-acting acyltransferases.
  Chembiochem, 7, 1206-1220.  
15546978 B.J.Bahnson (2004).
An atomic-resolution mechanism of 3-hydroxy-3-methylglutaryl-CoA synthase.
  Proc Natl Acad Sci U S A, 101, 16399-16400.  
15498869 M.J.Theisen, I.Misra, D.Saadat, N.Campobasso, H.M.Miziorko, and D.H.Harrison (2004).
3-hydroxy-3-methylglutaryl-CoA synthase intermediate complex observed in "real-time".
  Proc Natl Acad Sci U S A, 101, 16442-16447.
PDB codes: 1xpk 1xpl 1xpm
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