1l1q
From Proteopedia
(New page: 200px<br /><applet load="1l1q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l1q, resolution 1.85Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1l1q.jpg|left|200px]]<br /><applet load="1l1q" size=" | + | [[Image:1l1q.jpg|left|200px]]<br /><applet load="1l1q" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1l1q, resolution 1.85Å" /> | caption="1l1q, resolution 1.85Å" /> | ||
'''Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine'''<br /> | '''Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine'''<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== | ||
| - | 1L1Q 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 SO4 and 9DA 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:// | + | 1L1Q 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=SO4:'>SO4</scene> and <scene name='pdbligand=9DA:'>9DA</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=1L1Q OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[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: SO4]] | [[Category: SO4]] | ||
| Line 28: | Line 28: | ||
[[Category: purine metabolism]] | [[Category: purine metabolism]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:22 2008'' |
Revision as of 11:40, 21 February 2008
|
Crystal Structure of APRTase from Giardia lamblia Complexed with 9-deazaadenine
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
1L1Q 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
Page seeded by OCA on Thu Feb 21 13:40:22 2008
