1oz0

CRYSTAL STRUCTURE OF THE HOMODIMERIC BIFUNCTIONAL TRANSFORMYLASE AND CYCLOHYDROLASE ENZYME AVIAN ATIC IN COMPLEX WITH A MULTISUBSTRATE ADDUCT INHIBITOR BETA-DADF.CRYSTAL STRUCTURE OF THE HOMODIMERIC BIFUNCTIONAL TRANSFORMYLASE AND CYCLOHYDROLASE ENZYME AVIAN ATIC IN COMPLEX WITH A MULTISUBSTRATE ADDUCT INHIBITOR BETA-DADF.

Structural highlights 1oz0 is a 2 chain structure with sequence from Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PUR9_CHICK Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis. 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 The penultimate catalytic step of the purine de novo synthesis pathway is the conversion of aminoimidazole-4-carboxamide ribonucleotide (AICAR) to 5-formyl-AICAR that requires the cofactor N(10)-formyl-tetrahydrofolate as the formyl donor. This reaction is catalyzed by the AICAR transformylase domain of the bifunctional enzyme AICAR transformylase/inosine monophosphate cyclohydrolase (ATIC). Identification of the location of the AICAR transformylase active site was previously elucidated from the crystal structure of the avian ATIC with bound substrate AICAR; however, due to the absence of any bound folate, the folate binding region of the active site could not be identified. Here, we have determined the homodimeric crystal structure of avian ATIC in complex with the ATIC-specific multisubstrate adduct inhibitor beta-DADF to 2.5 A resolution. Beta-DADF encompasses both the AICAR and folate moieties into a single covalently linked entity, thereby allowing for the characterization of the folate binding pocket of the AICAR transformylase active site. Beta-DADF is intimately bound at the dimer interface of the transformylase domains with the majority of AICAR moiety interactions occurring within one subunit, whereas the primary interactions to the folate occur with the opposing subunit. The crystal structure suggests that a buried Lys(267) is transiently protonated during formyl transfer allowing for the stabilization of the oxyanion transition state and subsequent protonation of N10 on the tetrahydrofolate leaving group. Furthermore, the beta-DADF-bound structure provides a more optimal three-dimensional scaffold to improve the design of specific antineoplastic agents. Structure of avian AICAR transformylase with a multisubstrate adduct inhibitor beta-DADF identifies the folate binding site.,Wolan DW, Greasley SE, Wall MJ, Benkovic SJ, Wilson IA Biochemistry. 2003 Sep 23;42(37):10904-14. PMID:12974624 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Bifunctional purine biosynthesis protein PURH

spinqualitylabelsall models 1oz0, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image