PDBsum entry 4i6w

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
373 a.a.
1CO ×2
SO4 ×4
GOL ×2
Waters ×707
PDB id:
Name: Oxidoreductase
Title: 3-hydroxy-3-methylglutaryl (hmg) coenzyme-a reductase comple thiomevalonate
Structure: 3-hydroxy-3-methylglutaryl-coenzyme a reductase. Chain: a, b. Synonym: hmg-coa reductase. Engineered: yes
Source: Pseudomonas mevalonii. Organism_taxid: 32044. Gene: mvaa. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.66Å     R-factor:   0.194     R-free:   0.218
Authors: C.N.Steussy,C.V.Stauffacher,T.Schmidt,J.W.Burgner Ii,V.W.Rod L.V.Wrensford,C.J.Critchelow,J.Min
Key ref: C.N.Steussy et al. (2013). A novel role for coenzyme A during hydride transfer in 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Biochemistry, 52, 5195-5205. PubMed id: 23802607 DOI: 10.1021/bi400335g
30-Nov-12     Release date:   17-Jul-13    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P13702  (MVAA_PSEMV) -  3-hydroxy-3-methylglutaryl-coenzyme A reductase
428 a.a.
373 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Hydroxymethylglutaryl-CoA reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Mevalonate Biosynthesis
      Reaction: (R)-mevalonate + CoA + 2 NAD+ = 3-hydroxy-3-methylglutaryl-CoA + 2 NADH
Bound ligand (Het Group name = 1CO)
matches with 81.82% similarity
+ CoA
+ 2 × NAD(+)
= 3-hydroxy-3-methylglutaryl-CoA
+ 2 × NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     oxidoreductase activity     5 terms  


DOI no: 10.1021/bi400335g Biochemistry 52:5195-5205 (2013)
PubMed id: 23802607  
A novel role for coenzyme A during hydride transfer in 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
C.N.Steussy, C.J.Critchelow, T.Schmidt, J.K.Min, L.V.Wrensford, J.W.Burgner, V.W.Rodwell, C.V.Stauffacher.
In this study, we take advantage of the ability of HMG-CoA reductase (HMGR) from Pseudomonas mevalonii to remain active while in its crystallized form to study the changing interactions between the ligands and protein as the first reaction intermediate is created. HMG-CoA reductase catalyzes one of the few double oxidation-reduction reactions in intermediary metabolism that take place in a single active site. Our laboratory has undertaken an exploration of this reaction space using structures of HMG-CoA reductase complexed with various substrate, nucleotide, product, and inhibitor combinations. With a focus in this publication on the first hydride transfer, our structures follow this reduction reaction as the enzyme converts the HMG-CoA thioester from a flat sp(2)-like geometry to a pyramidal thiohemiacetal configuration consistent with a transition to an sp(3) orbital. This change in the geometry propagates through the coenzyme A (CoA) ligand whose first amide bond is rotated 180° where it anchors a web of hydrogen bonds that weave together the nucleotide, the reaction intermediate, the enzyme, and the catalytic residues. This creates a stable intermediate structure prepared for nucleotide exchange and the second reduction reaction within the HMG-CoA reductase active site. Identification of this reaction intermediate provides a template for the development of an inhibitor that would act as an antibiotic effective against the HMG-CoA reductase of methicillin-resistant Staphylococcus aureus.