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Crystal structures of penicillin-binding proteins 4 and 5 from Haemophilus influenzae
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Kawai, Fumihiro, Clarke, Thomas B., Roper, David I., Han, Gab-Jo, Hwang, Kwang Yeon, Unzai, Satoru, Obayashi, Eiji, Park, Sam-Yong and Tame, Jeremy R. H. (2010) Crystal structures of penicillin-binding proteins 4 and 5 from Haemophilus influenzae. Journal of Molecular Biology, Vol.396 (No.3). pp. 634-645. doi:10.1016/j.jmb.2009.11.055 ISSN 0022-2836.
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Official URL: http://dx.doi.org/10.1016/j.jmb.2009.11.055
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. (C) 2009 Elsevier Ltd. All rights reserved.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
Journal or Publication Title: | Journal of Molecular Biology | ||||
Publisher: | Academic Press | ||||
ISSN: | 0022-2836 | ||||
Official Date: | 26 February 2010 | ||||
Dates: |
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Volume: | Vol.396 | ||||
Number: | No.3 | ||||
Number of Pages: | 12 | ||||
Page Range: | pp. 634-645 | ||||
DOI: | 10.1016/j.jmb.2009.11.055 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Funder: | Ministry of Education, Culture, Sports, Science and Technology of Japan |
Data sourced from Thomson Reuters' Web of Knowledge
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