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PDBsum entry 1h3b

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protein ligands Protein-protein interface(s) links
Isomerase PDB id
1h3b
Jmol
Contents
Protein chains
620 a.a. *
Ligands
C8E ×3
R46 ×3
Waters ×208
* Residue conservation analysis
PDB id:
1h3b
Name: Isomerase
Title: Squalene-hopene cyclase
Structure: Squalene--hopene cyclase. Chain: a, b, c. Synonym: shc. Engineered: yes
Source: Alicyclobacillus acidocaldarius. Organism_taxid: 405212. Expressed in: escherichia coli k-12. Expression_system_taxid: 83333. Expression_system_variant: jm105. Other_details: thermostable, acidophilic
Biol. unit: Dimer (from PDB file)
Resolution:
2.80Å     R-factor:   0.206     R-free:   0.250
Authors: A.Lenhart,D.J.Reinert,W.A.Weihofen,J.D.Aebi,H.Dehmlow, O.H.Morand,G.E.Schulz
Key ref: A.Lenhart et al. (2003). Binding structures and potencies of oxidosqualene cyclase inhibitors with the homologous squalene-hopene cyclase. J Med Chem, 46, 2083-2092. PubMed id: 12747780 DOI: 10.1021/jm0211218
Date:
25-Aug-02     Release date:   21-Aug-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P33247  (SQHC_ALIAD) -  Squalene--hopene cyclase
Seq:
Struc:
 
Seq:
Struc:
631 a.a.
620 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.4.2.1.129  - Squalene--hopanol cyclase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hopan-22-ol = squalene + H2O
Hopan-22-ol
= squalene
+ H(2)O
   Enzyme class 3: E.C.5.4.99.17  - Squalene--hopene cyclase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: Squalene = hop-2229-ene
Squalene
= hop-22(29)-ene
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     hopanoid biosynthetic process   1 term 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm0211218 J Med Chem 46:2083-2092 (2003)
PubMed id: 12747780  
 
 
Binding structures and potencies of oxidosqualene cyclase inhibitors with the homologous squalene-hopene cyclase.
A.Lenhart, D.J.Reinert, J.D.Aebi, H.Dehmlow, O.H.Morand, G.E.Schulz.
 
  ABSTRACT  
 
The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the structures were elucidated by X-ray diffraction analyses. All inhibitors were bound in the large active center cavity. The detailed binding structures are presented and discussed in the light of the IC50 values of these 11 as well as 17 other inhibitors. They provide a consistent picture for the inhibition of the bacterial enzyme and can be used to adjust and improve homology models of the human enzyme. The detailed active center structures of the two enzymes are too different to show an IC50 correlation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21315634 S.Z.Grinter, Y.Liang, S.Y.Huang, S.M.Hyder, and X.Zou (2011).
An inverse docking approach for identifying new potential anti-cancer targets.
  J Mol Graph Model, 29, 795-799.  
19440746 R.J.Cenedella (2009).
Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes.
  Lipids, 44, 477-487.  
18367444 A.N.Eddine, J.P.von Kries, M.V.Podust, T.Warrier, S.H.Kaufmann, and L.M.Podust (2008).
X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51).
  J Biol Chem, 283, 15152-15159.
PDB code: 2vku
17846131 L.M.Podust, J.P.von Kries, A.N.Eddine, Y.Kim, L.V.Yermalitskaya, R.Kuehne, H.Ouellet, T.Warrier, M.Alteköster, J.S.Lee, J.Rademann, H.Oschkinat, S.H.Kaufmann, and M.R.Waterman (2007).
Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography.
  Antimicrob Agents Chemother, 51, 3915-3923.
PDB codes: 2bz9 2ci0 2cib
17154325 S.Oliaro-Bosso, F.Viola, S.Taramino, S.Tagliapietra, A.Barge, G.Cravotto, and G.Balliano (2007).
Inhibitory Effect of Umbelliferone Aminoalkyl Derivatives on Oxidosqualene Cyclases from S. cerevisiae, T. cruzi, P. carinii, H. sapiens, and A. thaliana: a Structure-Activity Study.
  ChemMedChem, 2, 226-233.  
15952226 K.Schärer, M.Morgenthaler, R.Paulini, U.Obst-Sander, D.W.Banner, D.Schlatter, J.Benz, M.Stihle, and F.Diederich (2005).
Quantification of cation-pi interactions in protein-ligand complexes: crystal-structure analysis of Factor Xa bound to a quaternary ammonium ion ligand.
  Angew Chem Int Ed Engl, 44, 4400-4404.
PDB code: 2bok
15929157 K.U.Wendt (2005).
Enzyme mechanisms for triterpene cyclization: new pieces of the puzzle.
  Angew Chem Int Ed Engl, 44, 3966-3971.  
16149744 R.J.Cenedella, P.S.Sexton, K.Krishnan, and D.F.Covey (2005).
Comparison of effects of U18666A and enantiomeric U18666A on sterol synthesis and induction of apoptosis.
  Lipids, 40, 635-640.  
16235265 S.Oliaro-Bosso, T.Schulz-Gasch, G.Balliano, and F.Viola (2005).
Access of the substrate to the active site of yeast oxidosqualene cyclase: an inhibition and site-directed mutagenesis approach.
  Chembiochem, 6, 2221-2228.  
15113001 D.J.Reinert, G.Balliano, and G.E.Schulz (2004).
Conversion of squalene to the pentacarbocyclic hopene.
  Chem Biol, 11, 121-126.
PDB code: 1ump
15691023 S.Oliaro-Bosso, F.Viola, S.Matsuda, G.Cravotto, S.Tagliapietra, and G.Balliano (2004).
Umbelliferone aminoalkyl derivatives as inhibitors of oxidosqualene cyclases from Saccharomyces cerevisiae, Trypanosoma cruzi, and Pneumocystis carinii.
  Lipids, 39, 1007-1012.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.