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http://purl.uniprot.org/citations/18787203http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18787203http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18787203http://www.w3.org/2000/01/rdf-schema#comment"In recent years, dihydrodipicolinate synthase (DHDPS, E.C. 4.2.1.52) has received considerable attention from a mechanistic and structural viewpoint. DHDPS catalyzes the reaction of (S)-aspartate-beta-semialdehyde with pyruvate, which is bound via a Schiff base to a conserved active-site lysine (Lys161 in the enzyme from Escherichia coli). To probe the mechanism of DHDPS, we have studied the inhibition of E. coli DHDPS by the substrate analog, beta-hydroxypyruvate. The K (i) was determined to be 0.21 (+/-0.02) mM, similar to that of the allosteric inhibitor, (S)-lysine, and beta-hydroxypyruvate was observed to cause time-dependent inhibition. The inhibitory reaction with beta-hydroxypyruvate could be qualitatively followed by mass spectrometry, which showed initial noncovalent adduct formation, followed by the slow formation of the covalent adduct. It is unclear whether beta-hydroxypyruvate plays a role in regulating the biosynthesis of meso-diaminopimelate and (S)-lysine in E. coli, although we note that it is present in vivo. The crystal structure of DHDPS complexed with beta-hydroxypyruvate was solved. The active site clearly showed the presence of the inhibitor covalently bound to the Lys161. Interestingly, the hydroxyl group of beta-hydroxypyruvate was hydrogen-bonded to the main-chain carbonyl of Ile203. This provides insight into the possible catalytic role played by this peptide unit, which has a highly strained torsion angle (omega approximately 201 degrees ). A survey of the known DHDPS structures from other organisms shows this distortion to be a highly conserved feature of the DHDPS active site, and we propose that this peptide unit plays a critical role in catalysis."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.org/dc/terms/identifier"doi:10.1110/ps.037440.108"xsd:string
http://purl.uniprot.org/citations/18787203http://purl.org/dc/terms/identifier"doi:10.1110/ps.037440.108"xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Dobson R.C."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Dobson R.C."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Gerrard J.A."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Gerrard J.A."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Jameson G.B."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Jameson G.B."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Pearce F.G."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Pearce F.G."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Perugini M.A."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Perugini M.A."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Devenish S.R."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Devenish S.R."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Griffin M.D."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Griffin M.D."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Hutton C.A."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/author"Hutton C.A."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/name"Protein Sci."xsd:string
http://purl.uniprot.org/citations/18787203http://purl.uniprot.org/core/name"Protein Sci."xsd:string