4LUS

alanine racemase [Clostridium difficile 630]

4LUS の概要

• エントリーDOI: 10.2210/pdb4lus/pdb
• 分子名称: Alanine racemase, GLYCEROL, 3,3',3''-phosphanetriyltripropanoic acid, ... (5 entities in total)
• 機能のキーワード: alanine racemase, isomerase
• 由来する生物種: Clostridium difficile; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 174843.54

構造登録者

Asojo, O.A. (登録日: 2013-07-25, 公開日: 2014-06-04, 最終更新日: 2023-12-06)

主引用文献

Asojo, O.A.,Nelson, S.K.,Mootien, S.,Lee, Y.,Rezende, W.C.,Hyman, D.A.,Matsumoto, M.M.,Reiling, S.,Kelleher, A.,Ledizet, M.,Koski, R.A.,Anthony, K.G.
Structural and biochemical analyses of alanine racemase from the multidrug-resistant Clostridium difficile strain 630.
Acta Crystallogr.,Sect.D, 70:1922-1933, 2014

PubMed Abstract: Clostridium difficile, a Gram-positive, spore-forming anaerobic bacterium, is the leading cause of infectious diarrhea among hospitalized patients. C. difficile is frequently associated with antibiotic treatment, and causes diseases ranging from antibiotic-associated diarrhea to life-threatening pseudomembranous colitis. The severity of C. difficile infections is exacerbated by the emergence of hypervirulent and multidrug-resistant strains, which are difficult to treat and are often associated with increased mortality rates. Alanine racemase (Alr) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the reversible racemization of L- and D-alanine. Since D-alanine is an essential component of the bacterial cell-wall peptidoglycan, and there are no known Alr homologs in humans, this enzyme is being tested as an antibiotic target. Cycloserine is an antibiotic that inhibits Alr. In this study, the catalytic properties and crystal structures of recombinant Alr from the virulent and multidrug-resistant C. difficile strain 630 are presented. Three crystal structures of C. difficile Alr (CdAlr), corresponding to the complex with PLP, the complex with cycloserine and a K271T mutant form of the enzyme with bound PLP, are presented. The structures are prototypical Alr homodimers with two active sites in which the cofactor PLP and cycloserine are localized. Kinetic analyses reveal that the K271T mutant CdAlr has the highest catalytic constants reported to date for any Alr. Additional studies are needed to identify the basis for the high catalytic activity. The structural and activity data presented are first steps towards using CdAlr for the development of structure-based therapeutics for C. difficile infections.

PubMed: 25004969
DOI: 10.1107/S1399004714009419

実験手法

X-RAY DIFFRACTION (2.1 Å)