1z7g
From Proteopedia
(New page: 200px<br /> <applet load="1z7g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z7g, resolution 1.90Å" /> '''Free human HGPRT'''...) |
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| - | [[Image:1z7g.gif|left|200px]]<br /> | + | [[Image:1z7g.gif|left|200px]]<br /><applet load="1z7g" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1z7g" size=" | + | |
caption="1z7g, resolution 1.90Å" /> | caption="1z7g, resolution 1.90Å" /> | ||
'''Free human HGPRT'''<br /> | '''Free human HGPRT'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the | + | Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the synthesis of the purine nucleoside monophosphates, IMP and GMP, by the addition of a 6-oxopurine base, either hypoxanthine or guanine, to the 1-beta-position of 5-phospho-alpha-d-ribosyl-1-pyrophosphate (PRib-PP). The mechanism is sequential, with PRib-PP binding to the free enzyme prior to the base. After the covalent reaction, pyrophosphate is released followed by the nucleoside monophosphate. A number of snapshots of the structure of this enzyme along the reaction pathway have been captured. These include the structure in the presence of the inactive purine base analogue, 7-hydroxy [4,3-d] pyrazolo pyrimidine (HPP) and PRib-PP.Mg2+, and in complex with IMP or GMP. The third structure is that of the immucillinHP.Mg(2+).PP(i) complex, a transition-state analogue. Here, the first crystal structure of free human HGPRT is reported to 1.9A resolution, showing that significant conformational changes have to occur for the substrate(s) to bind and for catalysis to proceed. Included in these changes are relative movement of subunits within the tetramer, rotation and extension of an active-site alpha-helix (D137-D153), reorientation of key active-site residues K68, D137 and K165, and the rearrangement of three active-site loops (100-128, 165-173 and 186-196). Toxoplasma gondii HGXPRT is the only other 6-oxopurine phosphoribosyltransferase structure solved in the absence of ligands. Comparison of this structure with human HGPRT reveals significant differences in the two active sites, including the structure of the flexible loop containing K68 (human) or K79 (T.gondii). |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Z7G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] Full crystallographic information is available from [http:// | + | 1Z7G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z7G OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Hypoxanthine phosphoribosyltransferase]] | [[Category: Hypoxanthine phosphoribosyltransferase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Brereton, I | + | [[Category: Brereton, I M.]] |
| - | [[Category: Guddat, L | + | [[Category: Guddat, L W.]] |
| - | [[Category: Jersey, J | + | [[Category: Jersey, J de.]] |
| - | [[Category: Keough, D | + | [[Category: Keough, D T.]] |
[[Category: flexibility]] | [[Category: flexibility]] | ||
[[Category: nucleotide binding]] | [[Category: nucleotide binding]] | ||
[[Category: trans cis peptide bond isomerization]] | [[Category: trans cis peptide bond isomerization]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:48 2008'' |
Revision as of 14:12, 21 February 2008
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Free human HGPRT
Contents |
Overview
Human hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the synthesis of the purine nucleoside monophosphates, IMP and GMP, by the addition of a 6-oxopurine base, either hypoxanthine or guanine, to the 1-beta-position of 5-phospho-alpha-d-ribosyl-1-pyrophosphate (PRib-PP). The mechanism is sequential, with PRib-PP binding to the free enzyme prior to the base. After the covalent reaction, pyrophosphate is released followed by the nucleoside monophosphate. A number of snapshots of the structure of this enzyme along the reaction pathway have been captured. These include the structure in the presence of the inactive purine base analogue, 7-hydroxy [4,3-d] pyrazolo pyrimidine (HPP) and PRib-PP.Mg2+, and in complex with IMP or GMP. The third structure is that of the immucillinHP.Mg(2+).PP(i) complex, a transition-state analogue. Here, the first crystal structure of free human HGPRT is reported to 1.9A resolution, showing that significant conformational changes have to occur for the substrate(s) to bind and for catalysis to proceed. Included in these changes are relative movement of subunits within the tetramer, rotation and extension of an active-site alpha-helix (D137-D153), reorientation of key active-site residues K68, D137 and K165, and the rearrangement of three active-site loops (100-128, 165-173 and 186-196). Toxoplasma gondii HGXPRT is the only other 6-oxopurine phosphoribosyltransferase structure solved in the absence of ligands. Comparison of this structure with human HGPRT reveals significant differences in the two active sites, including the structure of the flexible loop containing K68 (human) or K79 (T.gondii).
Disease
Known diseases associated with this structure: HPRT-related gout OMIM:[308000], Lesch-Nyhan syndrome, 300322, OMIM:[308000]
About this Structure
1Z7G is a Single protein structure of sequence from Homo sapiens. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Full crystallographic information is available from OCA.
Reference
The crystal structure of free human hypoxanthine-guanine phosphoribosyltransferase reveals extensive conformational plasticity throughout the catalytic cycle., Keough DT, Brereton IM, de Jersey J, Guddat LW, J Mol Biol. 2005 Aug 5;351(1):170-81. PMID:15990111
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