4PPR

Crystal structure of Mycobacterium tuberculosis D,D-peptidase Rv3330 in complex with meropenem

4PPR の概要

• エントリーDOI: 10.2210/pdb4ppr/pdb
• 関連するPDBエントリー: 4P0M
• 分子名称: Penicillin-binding protein DacB1, (4R,5S)-3-{[(3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-5-[(2S,3R)-3-hydroxy-1-oxobutan-2-yl]-4-methyl-4,5-d ihydro-1H-pyrrole-2-carboxylic acid (3 entities in total)
• 機能のキーワード: structural genomics, niaid, national institute of allergy and infectious diseases, tb structural genomics consortium, tbsgc, penicillin-binding protein, peptidoglycan d, d-peptidase, hydrolase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35100.28

構造登録者

Prigozhin, D.M.,Huizar, J.P.,Mavrici, D.,Alber, T.,TB Structural Genomics Consortium (TBSGC) (登録日: 2014-02-27, 公開日: 2014-11-05, 最終更新日: 2024-11-06)

主引用文献

Prigozhin, D.M.,Krieger, I.V.,Huizar, J.P.,Mavrici, D.,Waldo, G.S.,Hung, L.W.,Sacchettini, J.C.,Terwilliger, T.C.,Alber, T.
Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis.
Plos One, 9:e116249-e116249, 2014

PubMed Abstract: Beta-lactam antibiotics target penicillin-binding proteins including several enzyme classes essential for bacterial cell-wall homeostasis. To better understand the functional and inhibitor-binding specificities of penicillin-binding proteins from the pathogen, Mycobacterium tuberculosis, we carried out structural and phylogenetic analysis of two predicted D,D-carboxypeptidases, Rv2911 and Rv3330. Optimization of Rv2911 for crystallization using directed evolution and the GFP folding reporter method yielded a soluble quadruple mutant. Structures of optimized Rv2911 bound to phenylmethylsulfonyl fluoride and Rv3330 bound to meropenem show that, in contrast to the nonspecific inhibitor, meropenem forms an extended interaction with the enzyme along a conserved surface. Phylogenetic analysis shows that Rv2911 and Rv3330 belong to different clades that emerged in Actinobacteria and are not represented in model organisms such as Escherichia coli and Bacillus subtilis. Clade-specific adaptations allow these enzymes to fulfill distinct physiological roles despite strict conservation of core catalytic residues. The characteristic differences include potential protein-protein interaction surfaces and specificity-determining residues surrounding the catalytic site. Overall, these structural insights lay the groundwork to develop improved beta-lactam therapeutics for tuberculosis.

PubMed: 25551456
DOI: 10.1371/journal.pone.0116249

実験手法

X-RAY DIFFRACTION (2 Å)