1zn8

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{{STRUCTURE_1zn8| PDB=1zn8 | SCENE= }}
{{STRUCTURE_1zn8| PDB=1zn8 | SCENE= }}
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'''Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution'''
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===Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution===
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==Overview==
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Adenine phosphoribosyltransferase (APRT) is an important enzyme component of the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida are unable to synthesize purines de novo and use the salvage pathway for the synthesis of purine bases rendering this biosynthetic pathway an attractive target for antiparasitic drug design. The recombinant human adenine phosphoribosyltransferase (hAPRT) structure was resolved in the presence of AMP in the active site to 1.76 A resolution and with the substrates PRPP and adenine simultaneously bound to the catalytic site to 1.83 A resolution. An additional structure was solved containing one subunit of the dimer in the apo-form to 2.10 A resolution. Comparisons of these three hAPRT structures with other 'type I' PRTases revealed several important features of this class of enzymes. Our data indicate that the flexible loop structure adopts an open conformation before and after binding of both substrates adenine and PRPP. Comparative analyses presented here provide structural evidence to propose the role of Glu104 as the residue that abstracts the proton of adenine N9 atom before its nucleophilic attack on the PRPP anomeric carbon. This work leads to new insights to the understanding of the APRT catalytic mechanism.
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(as it appears on PubMed at http://www.pubmed.gov), where 18399692 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18399692}}
==Disease==
==Disease==
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[[Category: Polymorphism]]
[[Category: Polymorphism]]
[[Category: Purine salvage]]
[[Category: Purine salvage]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:23:21 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:36:17 2008''

Revision as of 12:36, 28 July 2008

Image:1zn8.png

Template:STRUCTURE 1zn8

Contents

Human Adenine Phosphoribosyltransferase Complexed with AMP, in Space Group P1 at 1.76 A Resolution

Template:ABSTRACT PUBMED 18399692

Disease

Known disease associated with this structure: Urolithiasis, 2,8-dihydroxyadenine OMIM:[102600]

About this Structure

1ZN8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural Complexes of Human Adenine Phosphoribosyltransferase Reveal Novel Features of the APRT Catalytic Mechanism., Silva CH, Silva M, Iulek J, Thiemann OH, J Biomol Struct Dyn. 2008 Jun;25(6):589-98. PMID:18399692

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