[en] AmpD is a bacterial amidase involved in the recycling of cell-wall fragments in Gram-negative bacteria. Inactivation of AmpD leads to derepression of beta-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.
Research center :
Research School of Chemistry Australian National University Canberra Center for Protein Engineering, Liege University Department of Medical Biochemistry and Biophysics Karolinska Institute, Stockholm
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Liepinsh, Edvards
Genereux, Catherine ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires > Parasitologie et pathologie des maladies parasitaires
Dehareng, Dominique ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Joris, Bernard ; Université de Liège - ULiège > Département des sciences de la vie > Physiologie et génétique bactériennes
Otting, Gottfried
Language :
English
Title :
NMR structure of Citrobacter freundii AmpD, comparison with bacteriophage T7 lysozyme and homology with PGRP domains.
Publication date :
2003
Journal title :
Journal of Molecular Biology
ISSN :
0022-2836
eISSN :
1089-8638
Publisher :
Academic Press, London, United Kingdom
Volume :
327
Issue :
4
Pages :
833-42
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique Swedish NMR Centre Sverige Vetenskapsrådet [SE] FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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