2WKS
Structure of Helicobacter pylori Type II Dehydroquinase with a new carbasugar-thiophene inhibitor.
Summary for 2WKS
| Entry DOI | 10.2210/pdb2wks/pdb |
| Related | 1J2Y 2C4V 2C4W 2C57 |
| Descriptor | 3-DEHYDROQUINATE DEHYDRATASE, (1R,4S,5R)-1,4,5-trihydroxy-3-[(5-methyl-1-benzothiophen-2-yl)methoxy]cyclohex-2-ene-1-carboxylic acid (3 entities in total) |
| Functional Keywords | aromatic amino acid biosynthesis, lyase, shikimic acid pathway, 3-dehydroquinate dehydratase |
| Biological source | HELICOBACTER PYLORI |
| Total number of polymer chains | 6 |
| Total formula weight | 113097.79 |
| Authors | Otero, J.M.,Guardado-Calvo, P.,Llamas-Saiz, A.L.,Prazeres, V.F.V.,Tizon, L.,Castedo, L.,Lamb, H.,Hawkins, A.R.,Gonzalez-Bello, C.,van Raaij, M.J. (deposition date: 2009-06-17, release date: 2009-11-24, Last modification date: 2023-12-13) |
| Primary citation | Prazeres, V.F.,Tizon, L.,Otero, J.M.,Guardado-Calvo, P.,Llamas-Saiz, A.L.,van Raaij, M.J.,Castedo, L.,Lamb, H.,Hawkins, A.R.,Gonzalez-Bello, C. Synthesis and biological evaluation of new nanomolar competitive inhibitors of Helicobacter pylori type II dehydroquinase. Structural details of the role of the aromatic moieties with essential residues. J. Med. Chem., 53:191-200, 2010 Cited by PubMed Abstract: The shikimic acid pathway is essential to many pathogens but absent in mammals. Enzymes in its pathway are therefore appropriate targets for the development of novel antibiotics. Dehydroquinase is the third enzyme of the pathway, catalyzing the reversible dehydratation of 3-dehydroquinic acid to form 3-dehydroshikimic acid. Here we present the synthesis of novel inhibitors with high affinity for Helicobacter pylori type II dehydroquinase and efficient inhibition characteristics. The structure of Helicobacter pylori type II dehydroquinase in complex with the most potent inhibitor shows that the aromatic functional group interacts with the catalytic Tyr22 by pi-stacking, expelling the Arg17 side chain, which is essential for catalysis, from the active site. The structure therefore explains the favorable properties of the inhibitor and will aid in design of improved antibiotics. PubMed: 19911771DOI: 10.1021/jm9010466 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.95 Å) |
Structure validation
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