3A3F

Crystal structure of penicillin binding protein 4 (dacB) from Haemophilus influenzae,complexed with novel beta-lactam (FMZ)

3A3F の概要

• エントリーDOI: 10.2210/pdb3a3f/pdb
• 関連するPDBエントリー: 3A3D 3A3E 3A3I 3A3J
• 分子名称: Penicillin-binding protein 4, (2R,4S)-5,5-dimethyl-2-[(1R)-2-oxo-1-({(2R)-2-[(2-oxoimidazolidin-1-yl)amino]-2-phenylacetyl}amino)ethyl]-1,3-thiazolidine-4-carboxylic acid (3 entities in total)
• 機能のキーワード: penicillin binding protein 4, pbp4, dacb, hydrolase
• 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: 100450.88

構造登録者

Kawai, F.,Roper, D.I.,Park, S.-Y.,Tame, J.R.H. (登録日: 2009-06-12, 公開日: 2009-12-22, 最終更新日: 2024-11-13)

主引用文献

Kawai, F.,Clarke, T.B.,Roper, D.I.,Han, G.-J.,Hwang, K.Y.,Unzai, S.,Obayashi, E.,Park, S.-Y.,Tame, J.R.H.
Crystal structures of penicillin-binding proteins 4 and 5 from Haemophilus influenzae
J.Mol.Biol., 396:634-645, 2010

PubMed Abstract: We have determined high-resolution apo crystal structures of two low molecular weight penicillin-binding proteins (PBPs), PBP4 and PBP5, from Haemophilus influenzae, one of the most frequently found pathogens in the upper respiratory tract of children. Novel beta-lactams with notable antimicrobial activity have been designed, and crystal structures of PBP4 complexed with ampicillin and two of the novel molecules have also been determined. Comparing the apo form with those of the complexes, we find that the drugs disturb the PBP4 structure and weaken X-ray diffraction, to very different extents. PBP4 has recently been shown to act as a sensor of the presence of penicillins in Pseudomonas aeruginosa, and our models offer a clue to the structural basis for this effect. Covalently attached penicillins press against a phenylalanine residue near the active site and disturb the deacylation step. The ready inhibition of PBP4 by beta-lactams compared to PBP5 also appears to be related to the weaker interactions holding key residues in a catalytically competent position.

PubMed: 19958776
DOI: 10.1016/j.jmb.2009.11.055

実験手法

X-RAY DIFFRACTION (2.1 Å)