1l1r
From Proteopedia
(New page: 200px<br /><applet load="1l1r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l1r, resolution 1.95Å" /> '''Crystal Structure of...) |
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| - | [[Image:1l1r.jpg|left|200px]]<br /><applet load="1l1r" size=" | + | [[Image:1l1r.jpg|left|200px]]<br /><applet load="1l1r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1l1r, resolution 1.95Å" /> | caption="1l1r, resolution 1.95Å" /> | ||
'''Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine, Mg2+ and PRPP'''<br /> | '''Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine, Mg2+ and PRPP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The adenine phosphoribosyltransferase (APRTase) from Giardia lamblia was | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1L1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Giardia_intestinalis Giardia intestinalis] with MG, 9DA and PRP 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:// | + | 1L1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Giardia_intestinalis Giardia intestinalis] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=9DA:'>9DA</scene> and <scene name='pdbligand=PRP:'>PRP</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=1L1R OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Giardia intestinalis]] | [[Category: Giardia intestinalis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Almo, S | + | [[Category: Almo, S C.]] |
| - | [[Category: Sarver, A | + | [[Category: Sarver, A E.]] |
| - | [[Category: Schramm, V | + | [[Category: Schramm, V L.]] |
[[Category: Shi, W.]] | [[Category: Shi, W.]] | ||
| - | [[Category: Tanaka, K | + | [[Category: Tanaka, K S.]] |
| - | [[Category: Wang, C | + | [[Category: Wang, C C.]] |
[[Category: 9DA]] | [[Category: 9DA]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: purine metabolism]] | [[Category: purine metabolism]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:25 2008'' |
Revision as of 11:40, 21 February 2008
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Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine, Mg2+ and PRPP
Overview
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.
About this Structure
1L1R is a Single protein structure of sequence from Giardia intestinalis with , and as ligands. Active as Adenine phosphoribosyltransferase, with EC number 2.4.2.7 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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