3ISZ

Crystal structure of mono-zinc form of succinyl-diaminopimelate desuccinylase from Haemophilus influenzae

3ISZ の概要

• エントリーDOI: 10.2210/pdb3isz/pdb
• 関連するPDBエントリー: 3IC1
• 分子名称: Succinyl-diaminopimelate desuccinylase, ZINC ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: dape, succinyl-diaminopimelate desuccinylase, zn-binding, metallopeptidase, structural genomics, psi-2, protein structure initiative, midwest center for structural genomics, mcsg, amino-acid biosynthesis, cobalt, diaminopimelate biosynthesis, hydrolase, lysine biosynthesis, metal-binding
• 由来する生物種: Haemophilus influenzae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 83118.85

構造登録者

Nocek, B.P.,Gillner, D.M.,Holz, R.C.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG) (登録日: 2009-08-27, 公開日: 2009-11-10, 最終更新日: 2023-09-06)

主引用文献

Nocek, B.P.,Gillner, D.M.,Fan, Y.,Holz, R.C.,Joachimiak, A.
Structural basis for catalysis by the mono- and dimetalated forms of the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase.
J.Mol.Biol., 397:617-626, 2010

PubMed Abstract: Biosynthesis of lysine and meso-diaminopimelic acid in bacteria provides essential components for protein synthesis and construction of the bacterial peptidoglycan cell wall. The dapE operon enzymes synthesize both meso-diaminopimelic acid and lysine and, therefore, represent potential targets for novel antibacterials. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase functions in a late step of the pathway and converts N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. Deletion of the dapE gene is lethal to Helicobacter pylori and Mycobacterium smegmatis, indicating that DapE's are essential for cell growth and proliferation. Since there are no similar pathways in humans, inhibitors that target DapE may have selective toxicity against only bacteria. A major limitation in developing antimicrobial agents that target DapE has been the lack of structural information. Herein, we report the high-resolution X-ray crystal structures of the DapE from Haemophilus influenzae with one and two zinc ions bound in the active site, respectively. These two forms show different activity. Based on these newly determined structures, we propose a revised catalytic mechanism of peptide bond cleavage by DapE enzymes. These structures provide important insight into catalytic mechanism of DapE enzymes as well as a structural foundation that is critical for the rational design of DapE inhibitors.

PubMed: 20138056
DOI: 10.1016/j.jmb.2010.01.062

実験手法

X-RAY DIFFRACTION (2 Å)