3k5i | pdb_00003k5i

Crystal structure of N5-carboxyaminoimidazole synthase from aspergillus clavatus in complex with ADP and 5-aminoimadazole ribonucleotide

spinqualitylabelsall models 3k5i, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3k5i is a 4 chain structure with sequence from Aspergillus clavatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: ADP, AIR, MG, NA, NHE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A1CII2_ASPCL 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 N(5)-Carboxyaminoimidazole ribonucleotide synthetase (N(5)-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N(5)-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report the cloning, crystallization, and three-dimensional structural analysis of Aspergillus clavatus N(5)-CAIR synthetase solved in the presence of either Mg(2)ATP or MgADP and AIR. These structures, determined to 2.1 and 2.0 A, respectively, revealed that AIR binds in a pocket analogous to that observed for other ATP-grasp enzymes involved in purine metabolism. On the basis of these models, a site-directed mutagenesis study was subsequently conducted that focused on five amino acid residues located in the active site region of the enzyme. These investigations demonstrated that Asp 153 and Lys 353 play critical roles in catalysis without affecting substrate binding. All other mutations affected substrate binding and, in some instances, catalysis as well. Taken together, the structural and kinetic data presented here suggest a catalytic mechanism whereby Mg(2)ATP and bicarbonate first react to form the unstable intermediate carboxyphosphate. This intermediate subsequently decarboxylates to CO(2) and inorganic phosphate, and the amino group of AIR, through general base assistance by Asp 153, attacks CO(2) to form N(5)-CAIR. Structural and functional studies of Aspergillus clavatus N(5)-carboxyaminoimidazole ribonucleotide synthetase .,Thoden JB, Holden HM, Paritala H, Firestine SM Biochemistry. 2010 Feb 2;49(4):752-60. PMID:20050602 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosylaminoimidazole carboxylase 3D structures

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