1SLY

COMPLEX OF THE 70-KDA SOLUBLE LYTIC TRANSGLYCOSYLASE WITH BULGECIN A

1SLY の概要

• エントリーDOI: 10.2210/pdb1sly/pdb
• 分子名称: 70-KDA SOLUBLE LYTIC TRANSGLYCOSYLASE, 4-O-(4-O-SULFONYL-N-ACETYLGLUCOSAMININYL)-5-METHYLHYDROXY-L-PROLINE-TAURINE (2 entities in total)
• 機能のキーワード: inhibitor-enzyme complex, lysozyme, peptidoglycan, hydrolase, glycosidase, periplasmic, glycosyltransferase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Periplasm: P03810
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 71113.11

構造登録者

Thunnissen, A.M.W.H.,Kalk, K.H.,Rozeboom, H.J.,Dijkstra, B.W. (登録日: 1995-08-02, 公開日: 1996-08-17, 最終更新日: 2024-10-30)

主引用文献

Thunnissen, A.M.,Rozeboom, H.J.,Kalk, K.H.,Dijkstra, B.W.
Structure of the 70-kDa soluble lytic transglycosylase complexed with bulgecin A. Implications for the enzymatic mechanism.
Biochemistry, 34:12729-12737, 1995

PubMed Abstract: 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.

PubMed: 7548026
DOI: 10.1021/bi00039a032

実験手法

X-RAY DIFFRACTION (2.8 Å)