2WKE
Crystal structure of the Actinomadura R39 DD-peptidase inhibited by 6- beta-iodopenicillanate.
Summary for 2WKE
| Entry DOI | 10.2210/pdb2wke/pdb |
| Related | 1W79 1W8Q 1W8Y 2VGJ 2VGK 2WIX |
| Descriptor | D-ALANYL-D-ALANINE CARBOXYPEPTIDASE, (3S)-2,2-dimethyl-3,4-dihydro-2H-1,4-thiazine-3,6-dicarboxylic acid, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | hydrolase, antibiotic resistance, actinomadura, penicillin binding, iodopenicillanate |
| Biological source | ACTINOMADURA SP. |
| Cellular location | Secreted: P39045 |
| Total number of polymer chains | 4 |
| Total formula weight | 194203.31 |
| Authors | Sauvage, E.,Herman, R.,Kerff, F.,Charlier, P. (deposition date: 2009-06-10, release date: 2009-12-01, Last modification date: 2023-12-13) |
| Primary citation | Sauvage, E.,Zervosen, A.,Dive, G.,Herman, R.,Amoroso, A.,Joris, B.,Fonze, E.,Pratt, R.F.,Luxen, A.,Charlier, P.,Kerff, F. Structural Basis of the Inhibition of Class a Beta-Lactamases and Penicillin-Binding Proteins by 6-Beta-Iodopenicillanate. J.Am.Chem.Soc., 131:15262-, 2009 Cited by PubMed Abstract: 6-Beta-halogenopenicillanates are powerful, irreversible inhibitors of various beta-lactamases and penicillin-binding proteins. Upon acylation of these enzymes, the inhibitors are thought to undergo a structural rearrangement associated with the departure of the iodide and formation of a dihydrothiazine ring, but, to date, no structural evidence has proven this. 6-Beta-iodopenicillanic acid (BIP) is shown here to be an active antibiotic against various bacterial strains and an effective inhibitor of the class A beta-lactamase of Bacillus subtilis BS3 (BS3) and the D,D-peptidase of Actinomadura R39 (R39). Crystals of BS3 and of R39 were soaked with a solution of BIP and their structures solved at 1.65 and 2.2 A, respectively. The beta-lactam and the thiazolidine rings of BIP are indeed found to be fused into a dihydrothiazine ring that can adopt two stable conformations at these active sites. The rearranged BIP is observed in one conformation in the BS3 active site and in two monomers of the asymmetric unit of R39, and is observed in the other conformation in the other two monomers of the asymmetric unit of R39. The BS3 structure reveals a new mode of carboxylate interaction with a class A beta-lactamase active site that should be of interest in future inhibitor design. PubMed: 19919161DOI: 10.1021/JA9051526 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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