Structure analysis of peptide deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa:: Snapshots of the oxygen sensitivity of peptide deformylase

被引：37

作者：

Kreusch, A ^{[1
]}

Spraggon, G ^{[1
]}

Lee, CC ^{[1
]}

Klock, H ^{[1
]}

McMullan, D ^{[1
]}

Ng, K ^{[1
]}

Shin, T ^{[1
]}

Vincent, J ^{[1
]}

Warner, I ^{[1
]}

Ericson, C ^{[1
]}

Lesley, SA ^{[1
]}

机构：

[1] Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2003年 / 330卷 / 02期

关键词：

peptide deformylase; crystal structure; drug design; antibiotic; metalloprotease;

D O I：

10.1016/S0022-2836(03)00596-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Peptide deformylase (PDF) has received considerable attention during the last few years as a potential target for a new type of antibiotics. It is an essential enzyme in eubacteria. for the removal of the formyl group from the N terminus of the nascent polypeptide chain. We have solved the X-ray structures of four members of this enzyme family, two from the Gram-positive pathogens Streptococcus pneumoniae and Staphylococcus aureus, and two from the Gram-negative bacteria Thermotoga maritima and Pseudomonas aeruginosa. Combined with the known structures from the Escherichia coli enzyme and the recently solved structure of the eukaryotic deformylase from Plasmodium falciparum, a complete picture of the peptide deformylase structure and function relationship is emerging. This understanding could help guide a more rational design of inhibitors. A structure-based comparison between PDFs reveals some conserved differences between type I and type II enzymes. Moreover, our structures provide insights into the known instability of PDF caused by oxidation of the metal-ligating cysteine residue. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：309 / 321

页数：13

共 45 条

[1] ON RELEASE OF FORMYL GROUP FROM NASCENT PROTEIN [J].