2XAD

Crystal structure of deacetylase-teicoplanin complex in biosynthesis pathway of teicoplanin

2XAD の概要

• エントリーDOI: 10.2210/pdb2xad/pdb
• 関連するPDBエントリー: 2WDX 2X9L 4K3T
• 関連するBIRD辞書のPRD_ID: PRD_000209
• 分子名称: N-ACYL GLM PEUDO-TEICOPLANIN DEACETYLASE, TEICOPLANIN, beta-D-mannopyranose, ... (7 entities in total)
• 機能のキーワード: oxidoreductase-antibiotic complex, antibiotic, a40926, glycopeptide, oxidoreductase/antibiotic
• 由来する生物種: ACTINOPLANES TEICHOMYCETICUS; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 128923.10

構造登録者

Chan, H.C.,Huang, Y.T.,Lyu, S.Y.,Huang, C.J.,Li, Y.S.,Liu, Y.C.,Chou, C.C.,Tsai, M.D.,Li, T.L. (登録日: 2010-03-31, 公開日: 2011-03-02, 最終更新日: 2025-04-09)

主引用文献

Chan, H.C.,Huang, Y.T.,Lyu, S.Y.,Huang, C.J.,Li, Y.S.,Liu, Y.C.,Chou, C.C.,Tsai, M.D.,Li, T.L.
Regioselective Deacetylation Based on Teicoplanin-Complexed Orf2 Crystal Structures.
Mol.Biosyst., 7:1224-, 2011

PubMed Abstract: Lipoglycopeptide antibiotics are more effective than vancomycin against MRSA as they carry an extra aliphatic acyl side chain on glucosamine (Glm) at residue 4 (r4). The biosynthesis of the r4 N-acyl Glc moiety at teicoplanin (Tei) or A40926 has been elucidated, in which the primary amine nucleophile of Glm is freed from the r4 GlcNac pseudo-Tei precursor by Orf2* for the subsequent acylation reaction to occur. In this report, two Orf2* structures in complex with β-D-octyl glucoside or Tei were solved. Of the complexed structures, the substrate binding site and a previously unknown hydrophobic cavity were revealed, wherein r4 GlcNac acts as the key signature for molecular recognition and the cavity allows substrates carrying longer acyl side chains in addition to the acetyl group. On the basis of the complexed structures, a triple-mutation mutant S98A/V121A/F193Y is able to regioselectively deacetylate r6 GlcNac pseudo-Tei instead of that at r4. Thereby, novel analogs can be made at the r6 sugar moiety.

PubMed: 21267472
DOI: 10.1039/C0MB00320D

実験手法

X-RAY DIFFRACTION (1.7 Å)