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| {{STRUCTURE_1l1q| PDB=1l1q | SCENE= }} | | {{STRUCTURE_1l1q| PDB=1l1q | SCENE= }} |
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- | '''Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine'''
| + | ===Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine=== |
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- | ==Overview==
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- | The adenine phosphoribosyltransferase (APRTase) from Giardia lamblia was co-crystallized with 9-deazaadenine and sulfate or with 9-deazaadenine and Mg-phosphoribosylpyrophosphate. The complexes were solved and refined to 1.85 and 1.95 A resolution. Giardia APRTase is a symmetric homodimer with the monomers built around Rossman fold cores, an element common to all known purine phosphoribosyltransferases. The catalytic sites are capped with a small hood domain that is unique to the APRTases. These structures reveal several features relevant to the catalytic function of APRTase: 1) a non-proline cis peptide bond (Glu(61)-Ser(62)) is required to form the pyrophosphate binding site in the APRTase.9dA.MgPRPP complex but is a trans peptide bond in the absence of pyrophosphate group, as observed in the APRTase.9dA.SO4 complex; 2) a catalytic site loop is closed and fully ordered in both complexes, with Glu(100) from the catalytic loop acting as the acid/base for protonation/deprotonation of N-7 of the adenine ring; 3) the pyrophosphoryl charge is neutralized by a single Mg2+ ion and Arg(63), in contrast to the hypoxanthine-guanine phosphoribosyltransferases, which use two Mg2+ ions; and 4) the nearest structural neighbors to APRTases are the orotate phosphoribosyltransferases, suggesting different paths of evolution for adenine relative to other purine PRTases. An overlap comparison of AMP and 9-deazaadenine plus Mg-PRPP at the catalytic sites of APRTases indicated that reaction coordinate motion involves a 2.1-A excursion of the ribosyl anomeric carbon, whereas the adenine ring and the 5-phosphoryl group remained fixed. G. lamblia APRTase therefore provides another example of nucleophilic displacement by electrophile migration.
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Giardia lamblia]] | | [[Category: Giardia lamblia]] |
| [[Category: Purine metabolism]] | | [[Category: Purine metabolism]] |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:26:32 2008'' | + | |
| + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:30:25 2008'' |
Revision as of 08:30, 2 July 2008
Template:STRUCTURE 1l1q
Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine
Template:ABSTRACT PUBMED 12171925
About this Structure
1L1Q is a Single protein structure of sequence from Giardia intestinalis. Full crystallographic information is available from OCA.
Reference
Closed site complexes of adenine phosphoribosyltransferase from Giardia lamblia reveal a mechanism of ribosyl migration., Shi W, Sarver AE, Wang CC, Tanaka KS, Almo SC, Schramm VL, J Biol Chem. 2002 Oct 18;277(42):39981-8. Epub 2002 Aug 8. PMID:12171925
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