Title of article :
NMR Structure of Citrobacter freundii AmpD, Comparison with Bacteriophage T7 Lysozyme and Homology with PGRP Domains
Author/Authors :
Edvards Liepinsh، نويسنده , , Catherine Généreux، نويسنده , , Dominique Dehareng، نويسنده , , Bernard Joris، نويسنده , , Nicholas E Dixon and Gottfried Otting، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2003
Abstract :
AmpD is a bacterial amidase involved in the recycling of cell-wall fragments in Gram-negative bacteria. Inactivation of AmpD leads to derepression of β-lactamase expression, presenting a major pathway for the acquisition of constitutive antibiotic resistance. Here, we report the NMR structure of AmpD from Citrobacter freundii (PDB accession code 1J3G). A deep substrate-binding pocket explains the observed specificity for low molecular mass substrates. The fold is related to that of bacteriophage T7 lysozyme. Both proteins bind zinc at a conserved site and require zinc for amidase activity, although the enzymatic mechanism seems to differ in detail. The structure-based sequence alignment identifies conserved features that are also conserved in the eukaryotic peptidoglycan recognition protein (PGRP) domains, including the zinc-coordination site in several of them. PGRP domains thus belong to the same fold family and, where zinc-binding residues are conserved, may have amidase activity. This hypothesis is supported by the observation that human serum N-acetylmuramyl-l-alanine amidase seems to be identical with a soluble form of human PGRP-L.
Keywords :
?-lactamase induction , AmpD , NMR structure , zinc amidase , peptidoglycan recognition protein domain
Journal title :
Journal of Molecular Biology
Journal title :
Journal of Molecular Biology