1ore
From Proteopedia
(New page: 200px<br /> <applet load="1ore" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ore, resolution 2.10Å" /> '''Human Adenine Phosp...) |
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| - | [[Image:1ore.gif|left|200px]]<br /> | + | [[Image:1ore.gif|left|200px]]<br /><applet load="1ore" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ore" size=" | + | |
caption="1ore, resolution 2.10Å" /> | caption="1ore, resolution 2.10Å" /> | ||
'''Human Adenine Phosphoribosyltransferase'''<br /> | '''Human Adenine Phosphoribosyltransferase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) is | + | In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) is present in all tissues and provides the only known mechanism for the metabolic salvage of adenine resulting from the polyamine biosynthesis pathway or from dietary sources. In humans, APRT deficiency results in serious kidney illness such as nephrolithiasis, interstitial nephritis, and chronic renal failure as a result of 2,8-dihydroxyadenine (DHA) precipitation in the renal interstitium. To address the molecular basis of DHA-urolithiasis, the recombinant human APRT was crystallized in complex with adenosine 5'-monophosphate (AMP). Refinement of X-ray diffraction data extended to 2.1 A resolution led to a final crystallographic R(factor) of 13.3% and an R(free) of 17.6%. This structure is composed of nine beta-strands and six alpha-helices, and the active site pocket opens slightly to accommodate the AMP product. The core of APRT is similar to that of other phosphoribosyltransferases (PRTases), although the adenine-binding domain is quite different. Structural comparisons between the human APRT and other "type I" PRTases of known structure revealed several important features of the biochemistry of PRTases. We propose that the residues located at positions corresponding to Leu159 and Ala131 in hAPRT are responsible for the base specificities of type I PRTases. The comparative analysis shown here also provides structural information for the mechanism by which mutations in the human APRT lead to DHA-urolithiasis. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ORE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL and AMP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenine_phosphoribosyltransferase Adenine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.7 2.4.2.7] Full crystallographic information is available from [http:// | + | 1ORE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=AMP:'>AMP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenine_phosphoribosyltransferase Adenine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.7 2.4.2.7] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Iulek, J.]] | [[Category: Iulek, J.]] | ||
[[Category: Oliva, G.]] | [[Category: Oliva, G.]] | ||
| - | [[Category: Silva, C | + | [[Category: Silva, C H.T P.]] |
[[Category: Silva, M.]] | [[Category: Silva, M.]] | ||
| - | [[Category: Thiemann, O | + | [[Category: Thiemann, O H.]] |
[[Category: AMP]] | [[Category: AMP]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: urolithiasis]] | [[Category: urolithiasis]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:20:48 2008'' |
Revision as of 12:20, 21 February 2008
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Human Adenine Phosphoribosyltransferase
Contents |
Overview
In mammals, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) is present in all tissues and provides the only known mechanism for the metabolic salvage of adenine resulting from the polyamine biosynthesis pathway or from dietary sources. In humans, APRT deficiency results in serious kidney illness such as nephrolithiasis, interstitial nephritis, and chronic renal failure as a result of 2,8-dihydroxyadenine (DHA) precipitation in the renal interstitium. To address the molecular basis of DHA-urolithiasis, the recombinant human APRT was crystallized in complex with adenosine 5'-monophosphate (AMP). Refinement of X-ray diffraction data extended to 2.1 A resolution led to a final crystallographic R(factor) of 13.3% and an R(free) of 17.6%. This structure is composed of nine beta-strands and six alpha-helices, and the active site pocket opens slightly to accommodate the AMP product. The core of APRT is similar to that of other phosphoribosyltransferases (PRTases), although the adenine-binding domain is quite different. Structural comparisons between the human APRT and other "type I" PRTases of known structure revealed several important features of the biochemistry of PRTases. We propose that the residues located at positions corresponding to Leu159 and Ala131 in hAPRT are responsible for the base specificities of type I PRTases. The comparative analysis shown here also provides structural information for the mechanism by which mutations in the human APRT lead to DHA-urolithiasis.
Disease
Known disease associated with this structure: Urolithiasis, 2,8-dihydroxyadenine OMIM:[102600]
About this Structure
1ORE is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Adenine phosphoribosyltransferase, with EC number 2.4.2.7 Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of human adenine phosphoribosyltransferase and its relation to DHA-urolithiasis., Silva M, Silva CH, Iulek J, Thiemann OH, Biochemistry. 2004 Jun 22;43(24):7663-71. PMID:15196008
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