1sly
From Proteopedia
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COMPLEX OF THE 70-KDA SOLUBLE LYTIC TRANSGLYCOSYLASE WITH BULGECIN A
Overview
Bulgecins are O-sulfonated glycopeptides that are able to enhance the, antibacterial activity of beta-lactam antibiotics. The 70-kDa soluble, lytic transglycosylase (SLT70) from Escherichia coli forms a specific, target of these compounds. Using X-ray crystallography, the, three-dimensional structure of a complex of SLT70 with bulgecin A has been, determined to 2.8-A resolution and refined to an R factor of 19.5%. The, model contains all 618 amino acids of SLT70 and a single molecule of bound, bulgecin, located in the active site of the enzyme. The glycopeptide, inhibitor is bound in an extended conformation occupying sites analogous, to the B, C, and D subsites of lysozyme. Upon binding of bulgecin, the, three-stranded antiparallel beta-sheet in the C domain shows a pronounced, shift toward the inhibitor. In subsite D, the proposed catalytic residue, Glu478 forms a hydrogen bond to the hydroxymethyl oxygen of the proline, part of bulgecin and interacts electrostatically with the proline NH2+, group. These interactions, in addition to the interactions observed for, the 2-acetamido group of the N-acetylglucosamine residue bound in subsite, C, may explain the strong inhibition of SLT70 activity by bulgecin, suggesting that bulgecin acts as an analogue of an oxocarbonium ion, intermediate in the reaction catalyzed by SLT70. The structure of the, SLT70--bulgecin A complex may be of assistance in the rational design of, novel antibiotics.
About this Structure
1SLY is a Single protein structure of sequence from Escherichia coli with BLG as ligand. Full crystallographic information is available from OCA.
Reference
Structure of the 70-kDa soluble lytic transglycosylase complexed with bulgecin A. Implications for the enzymatic mechanism., Thunnissen AM, Rozeboom HJ, Kalk KH, Dijkstra BW, Biochemistry. 1995 Oct 3;34(39):12729-37. PMID:7548026
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