2a6n

Dihydrodipicolinate synthase (E. coli)- mutant R138A

spinqualitylabelsall models 2a6n, resolution 1.94Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2a6n is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: K Gene: dapA ("Bacillus coli" Migula 1895) Activity: 4-hydroxy-tetrahydrodipicolinate synthase, with EC number 4.3.3.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DAPA_ECOLI] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA). 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 PubMed In plants and bacteria, the branch point of (S)-lysine biosynthesis is the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate, a reaction catalyzed by dihydrodipicolinate synthase (DHDPS, EC 4.2.1.52). It has been proposed that Arg138, a residue situated at the entrance to the active site of DHDPS, is responsible for binding the carboxyl of (S)-ASA and may additionally be involved in the mechanism of (S)-lysine inhibition. This study tests these assertions by mutation of Arg138 to both histidine and alanine. Following purification, DHDPS-R138H and DHDPS-R138A each showed severely compromised activity (approximately 0.1% that of the wild type), and the apparent Michaelis-Menten constant for (S)-ASA in each mutant, calculated using a pseudo-single substrate analysis, was significantly higher than that of the wild type. This provides good evidence that Arg138 is indeed essential for catalysis and plays a key role in substrate binding. To test whether structural changes could account for the change in kinetic behavior, the solution structure was probed via far-UV circular dichroism, confirming that the mutations at position 138 did not modify secondary structure. The crystal structures of both mutant enzymes were determined, confirming the presence of the mutations and suggesting that Arg138 plays an important role in catalysis: the stabilization of the catalytic triad residues, a motif we have previously demonstrated to be essential for activity. In addition, the role of Arg138 in (S)-lysine inhibition was examined. Both mutant enzymes showed the same IC(50) values as the wild type but different partial inhibition patterns, from which it is concluded that arginine 138 is not essential for (S)-lysine inhibition. Role of arginine 138 in the catalysis and regulation of Escherichia coli dihydrodipicolinate synthase.,Dobson RC, Devenish SR, Turner LA, Clifford VR, Pearce FG, Jameson GB, Gerrard JA Biochemistry. 2005 Oct 4;44(39):13007-13. PMID:16185069 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dihydrodipicolinate synthase

Proteopedia Page Contributors and Editors (what is this?)

OCA