Please use this identifier to cite or link to this item:
https://doi.org/10.1371/journal.pone.0066936
DC Field | Value | |
---|---|---|
dc.title | Substrate Channel Flexibility in Pseudomonas aeruginosa MurB Accommodates Two Distinct Substrates | |
dc.contributor.author | Chen M.W. | |
dc.contributor.author | Lohkamp B. | |
dc.contributor.author | Schnell R. | |
dc.contributor.author | Lescar J. | |
dc.contributor.author | Schneider G. | |
dc.date.accessioned | 2020-03-31T03:01:41Z | |
dc.date.available | 2020-03-31T03:01:41Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Chen M.W., Lohkamp B., Schnell R., Lescar J., Schneider G. (2013). Substrate Channel Flexibility in Pseudomonas aeruginosa MurB Accommodates Two Distinct Substrates. PLoS ONE 8 (6) : e66936. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0066936 | |
dc.identifier.issn | 19326203 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/166195 | |
dc.description.abstract | Biosynthesis of UDP-N-acetylmuramic acid in bacteria is a committed step towards peptidoglycan production. In an NADPH- and FAD-dependent reaction, the UDP-N-acetylglucosamine-enolpyruvate reductase (MurB) reduces UDP-N-acetylglucosamine-enolpyruvate to UDP-N-acetylmuramic acid. We determined the three-dimensional structures of the ternary complex of Pseudomonas aeruginosa MurB with FAD and NADP+ in two crystal forms to resolutions of 2.2 and 2.1 Å, respectively, to investigate the structural basis of the first half-reaction, hydride transfer from NADPH to FAD. The nicotinamide ring of NADP+ stacks against the si face of the isoalloxazine ring of FAD, suggesting an unusual mode of hydride transfer to flavin. Comparison with the structure of the Escherichia coli MurB complex with UDP-N-acetylglucosamine-enolpyruvate shows that both substrates share the binding site located between two lobes of the substrate-binding domain III, consistent with a ping pong mechanism with sequential substrate binding. The nicotinamide and the enolpyruvyl moieties are strikingly well-aligned upon superimposition, both positioned for hydride transfer to and from FAD. However, flexibility of the substrate channel allows the non-reactive parts of the two substrates to bind in different conformations. A potassium ion in the active site may assist in substrate orientation and binding. These structural models should help in structure-aided drug design against MurB, which is essential for cell wall biogenesis and hence bacterial survival. © 2013 Chen et al. | |
dc.publisher | Public Library of Science | |
dc.source | Unpaywall 20200320 | |
dc.subject | bacterial enzyme | |
dc.subject | flavine adenine nucleotide | |
dc.subject | nicotinamide | |
dc.subject | nicotinamide adenine dinucleotide phosphate | |
dc.subject | potassium ion | |
dc.subject | unclassified drug | |
dc.subject | uridine diphosphate n acetylglucosamine enolpyruvate reductase | |
dc.subject | bacterial protein | |
dc.subject | flavine adenine nucleotide | |
dc.subject | nicotinamide adenine dinucleotide phosphate | |
dc.subject | oxidoreductase | |
dc.subject | potassium | |
dc.subject | recombinant protein | |
dc.subject | UDP-N-acetylglucosamine-enolpyruvate | |
dc.subject | uridine diphosphate n acetylglucosamine | |
dc.subject | article | |
dc.subject | binding site | |
dc.subject | complex formation | |
dc.subject | controlled study | |
dc.subject | crystal structure | |
dc.subject | enzyme kinetics | |
dc.subject | enzyme localization | |
dc.subject | enzyme substrate | |
dc.subject | Escherichia coli | |
dc.subject | nonhuman | |
dc.subject | nucleotide sequence | |
dc.subject | protein conformation | |
dc.subject | protein structure | |
dc.subject | Pseudomonas aeruginosa | |
dc.subject | species comparison | |
dc.subject | amino acid sequence | |
dc.subject | analogs and derivatives | |
dc.subject | biosynthesis | |
dc.subject | chemistry | |
dc.subject | enzyme active site | |
dc.subject | enzyme specificity | |
dc.subject | enzymology | |
dc.subject | genetics | |
dc.subject | isolation and purification | |
dc.subject | metabolism | |
dc.subject | molecular dynamics | |
dc.subject | Pseudomonas aeruginosa | |
dc.subject | sequence alignment | |
dc.subject | X ray crystallography | |
dc.subject | Bacteria (microorganisms) | |
dc.subject | Escherichia coli | |
dc.subject | Pseudomonas aeruginosa | |
dc.subject | Amino Acid Sequence | |
dc.subject | Bacterial Proteins | |
dc.subject | Binding Sites | |
dc.subject | Catalytic Domain | |
dc.subject | Crystallography, X-Ray | |
dc.subject | Escherichia coli | |
dc.subject | Flavin-Adenine Dinucleotide | |
dc.subject | Molecular Dynamics Simulation | |
dc.subject | NADP | |
dc.subject | Oxidoreductases | |
dc.subject | Potassium | |
dc.subject | Pseudomonas aeruginosa | |
dc.subject | Recombinant Proteins | |
dc.subject | Sequence Alignment | |
dc.subject | Substrate Specificity | |
dc.subject | Uridine Diphosphate N-Acetylglucosamine | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1371/journal.pone.0066936 | |
dc.description.sourcetitle | PLoS ONE | |
dc.description.volume | 8 | |
dc.description.issue | 6 | |
dc.description.page | e66936 | |
Appears in Collections: | Staff Publications Elements |
Show simple item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1371_journal_pone_0066936.pdf | 3.98 MB | Adobe PDF | OPEN | None | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.