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Crystal structure of dihydrodipicolinate synthase from the pathogen Neisseria meningitidisCrystal structure of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis
Structural highlights
FunctionDAPA_NEIMB Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNeisseria meningitidis is an obligate commensal bacterium of humans, and also an important human pathogen. To facilitate future drug studies, we report here the biochemical and structural characterisation of a key enzyme in (S)-lysine biosynthesis, dihydrodipicolinate synthase (DHDPS), from N. meningitidis (NmeDHDPS). X-ray crystallography revealed only minor structural differences between NmeDHDPS and the enzyme from E. coli at the active and allosteric effector sites. The catalytic capabilities of NmeDHDPS are similar to those of the enzyme from E. coli, but intriguingly NmeDHDPS is subject to substrate inhibition by high concentrations of the second substrate, (S)-aspartate semialdehyde, and is also significantly more sensitive to feedback inhibition by (S)-lysine. This heightened sensitivity to inhibition at both active and allosteric sites suggests that it may be possible to target DHDPS from N. meningitidis for antibiotic development. Cloning and characterisation of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis.,Devenish SR, Huisman FH, Parker EJ, Hadfield AT, Gerrard JA Biochim Biophys Acta. 2009 Aug;1794(8):1168-74. Epub 2009 Feb 21. PMID:19236959[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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