1m9n

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{{STRUCTURE_1m9n| PDB=1m9n | SCENE= }}
{{STRUCTURE_1m9n| PDB=1m9n | SCENE= }}
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'''CRYSTAL STRUCTURE OF THE HOMODIMERIC BIFUNCTIONAL TRANSFORMYLASE AND CYCLOHYDROLASE ENZYME AVIAN ATIC IN COMPLEX WITH AICAR AND XMP AT 1.93 ANGSTROMS.'''
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===CRYSTAL STRUCTURE OF THE HOMODIMERIC BIFUNCTIONAL TRANSFORMYLASE AND CYCLOHYDROLASE ENZYME AVIAN ATIC IN COMPLEX WITH AICAR AND XMP AT 1.93 ANGSTROMS.===
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==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Homodimer]]
[[Category: Homodimer]]
[[Category: Impch domain = alpha/beta/alpha]]
[[Category: Impch domain = alpha/beta/alpha]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:30:23 2008''

Revision as of 20:30, 2 July 2008

Template:STRUCTURE 1m9n

CRYSTAL STRUCTURE OF THE HOMODIMERIC BIFUNCTIONAL TRANSFORMYLASE AND CYCLOHYDROLASE ENZYME AVIAN ATIC IN COMPLEX WITH AICAR AND XMP AT 1.93 ANGSTROMS.

Template:ABSTRACT PUBMED 12501179

About this Structure

1M9N is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.

Reference

Structural insights into the avian AICAR transformylase mechanism., Wolan DW, Greasley SE, Beardsley GP, Wilson IA, Biochemistry. 2002 Dec 31;41(52):15505-13. PMID:12501179

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