2XAD

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

Summary for 2XAD

• Entry DOI: 10.2210/pdb2xad/pdb
• Related: 2WDX 2X9L 4K3T
• Related PRD ID: PRD_000209
• Descriptor: N-ACYL GLM PEUDO-TEICOPLANIN DEACETYLASE, TEICOPLANIN, beta-D-mannopyranose, ... (7 entities in total)
• Functional Keywords: oxidoreductase-antibiotic complex, antibiotic, a40926, glycopeptide, oxidoreductase/antibiotic
• Biological source: ACTINOPLANES TEICHOMYCETICUS; More
• Total number of polymer chains: 8
• Total formula weight: 128923.10

Authors

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. (deposition date: 2010-03-31, release date: 2011-03-02, Last modification date: 2025-04-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.7 Å)