1BSJ

COBALT DEFORMYLASE INHIBITOR COMPLEX FROM E.COLI

Summary for 1BSJ

• Entry DOI: 10.2210/pdb1bsj/pdb
• Descriptor: PROTEIN (PEPTIDE DEFORMYLASE), COBALT (II) ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: deformylase, inhibitor, metalloproteinase, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 1
• Total formula weight: 19825.56

Authors

Hao, B.,Gong, W.,Rajagopalan, P.T.,Hu, Y.,Pei, D.,Chan, M.K. (deposition date: 1998-08-28, release date: 2000-04-15, Last modification date: 2023-08-09)

Primary citation

Hao, B.,Gong, W.,Rajagopalan, P.T.,Zhou, Y.,Pei, D.,Chan, M.K.
Structural basis for the design of antibiotics targeting peptide deformylase.
Biochemistry, 38:4712-4719, 1999

PubMed Abstract: While protein synthesis in bacteria begins with a formylated methionine, the formyl group of the nascent polypeptide is removed by peptide deformylase. Since eukaryotic protein synthesis does not involve formylation and deformylation at the N-terminus, there has been increasing interest in peptide deformylase as a potential target for antibacterial chemotherapy. Toward this end and to aid in the design of effective antibiotics targeting peptide deformylase, the structures of the protein-inhibitor complexes of both the cobalt and the zinc containing Escherichia coli peptide deformylase bound to the transition-state analogue, (S)-2-O-(H-phosphonoxy)-L-caproyl-L-leucyl-p-nitroanilide (PCLNA), have been determined. The proteins for both deformylase-inhibitor complexes show basically the same fold as for the native enzyme. The PCLNA inhibitor adopts an extended conformation and fits nicely into a hydrophobic cavity located near the metal site. On the basis of these structures, guidelines for the design of high-affinity deformylase inhibitors are suggested. As our results show that the protein residues which interact with the PCLNA inhibitor are conserved over a wide variety of species, we suggest that antibiotics targeting deformylase could have wide applicability.

PubMed: 10200158
DOI: 10.1021/bi982594c

Experimental method

X-RAY DIFFRACTION (3 Å)