1M9N
CRYSTAL STRUCTURE OF THE HOMODIMERIC BIFUNCTIONAL TRANSFORMYLASE AND CYCLOHYDROLASE ENZYME AVIAN ATIC IN COMPLEX WITH AICAR AND XMP AT 1.93 ANGSTROMS.
Summary for 1M9N
| Entry DOI | 10.2210/pdb1m9n/pdb |
| Related | 1G8M |
| Descriptor | AICAR TRANSFORMYLASE-IMP CYCLOHYDROLASE, POTASSIUM ION, AMINOIMIDAZOLE 4-CARBOXAMIDE RIBONUCLEOTIDE, ... (5 entities in total) |
| Functional Keywords | homodimer, 2 functional domains; impch domain = alpha/beta/alpha; aicar tfase = 2 alpha/beta/alpha domains, 1 alpha + beta domain, transferase, hydrolase |
| Biological source | Gallus gallus (chicken) |
| Total number of polymer chains | 2 |
| Total formula weight | 134823.22 |
| Authors | Wolan, D.W.,Greasly, S.E.,Beardsley, G.P.,Wilson, I.A. (deposition date: 2002-07-29, release date: 2003-01-07, Last modification date: 2024-02-14) |
| Primary citation | Wolan, D.W.,Greasly, S.E.,Beardsley, G.P.,Wilson, I.A. Structural Insights into the Avian AICAR Transformylase Mechanism. Biochemistry, 41:15505-15513, 2002 Cited by PubMed Abstract: ATIC encompasses both AICAR transformylase and IMP cyclohydrolase activities that are responsible for the catalysis of the penultimate and final steps of the purine de novo synthesis pathway. The formyl transfer reaction catalyzed by the AICAR Tfase domain is substantially more demanding than that catalyzed by the other folate-dependent enzyme of the purine biosynthesis pathway, GAR transformylase. Identification of the AICAR Tfase active site and key catalytic residues is essential to elucidate how the non-nucleophilic AICAR amino group is activated for formyl transfer. Hence, the crystal structure of dimeric avian ATIC was determined as a complex with the AICAR Tfase substrate AICAR, as well as with an IMP cyclohydrolase inhibitor, XMP, to 1.93 A resolution. AICAR is bound at the dimer interface of the transformylase domains and forms an extensive hydrogen bonding network with a multitude of active site residues. The crystal structure suggests that the conformation of the 4-carboxamide of AICAR is poised to increase the nucleophilicity of the C5 amine, while proton abstraction occurs via His(268) concomitant with formyl transfer. Lys(267) is likely to be involved in the stabilization of the anionic formyl transfer transition state and in subsequent protonation of the THF leaving group. PubMed: 12501179DOI: 10.1021/bi020505x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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