2jbm
From Proteopedia
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Human quinolinate phosphoribosyltransferase (EC 2.4.2.19) (hQPRTase) is a | + | Human quinolinate phosphoribosyltransferase (EC 2.4.2.19) (hQPRTase) is a member of the type II phosphoribosyltransferase family involved in the catabolism of quinolinic acid (QA). It catalyses the formation of nicotinic acid mononucleotide from quinolinic acid, which involves a phosphoribosyl transfer reaction followed by decarboxylation. hQPRTase has been implicated in a number of neurological conditions and in order to study it further, we have carried out structural and kinetic studies on recombinant hQPRTase. The structure of the fully active enzyme overexpressed in Escherichia coli was solved using multiwavelength methods to a resolution of 2.0 A. hQPRTase has a alpha/beta barrel fold sharing a similar overall structure with the bacterial QPRTases. The active site of hQPRTase is located at an alpha/beta open sandwich structure that serves as a cup for the alpha/beta barrel of the adjacent subunit with a QA binding site consisting of three arginine residues (R102, R138 and R161) and two lysine residues (K139 and K171). Mutation of these residues affected substrate binding or abolished the enzymatic activity. The kinetics of the human enzyme are different to the bacterial enzymes studied, hQPRTase is inhibited competitively and non-competitively by one of its substrates, 5-phosphoribosylpyrophosphate (PRPP). The human enzyme adopts a hexameric arrangement, which places the active sites in close proximity to each other. |
==About this Structure== | ==About this Structure== | ||
| Line 10: | Line 10: | ||
==Reference== | ==Reference== | ||
| - | Structural and | + | Structural and kinetic characterization of quinolinate phosphoribosyltransferase (hQPRTase) from homo sapiens., Liu H, Woznica K, Catton G, Crawford A, Botting N, Naismith JH, J Mol Biol. 2007 Oct 26;373(3):755-63. Epub 2007 Aug 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17868694 17868694] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Nicotinate-nucleotide diphosphorylase (carboxylating)]] | [[Category: Nicotinate-nucleotide diphosphorylase (carboxylating)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Liu, H.]] | [[Category: Liu, H.]] | ||
| - | [[Category: Naismith, J | + | [[Category: Naismith, J H.]] |
[[Category: SRT]] | [[Category: SRT]] | ||
[[Category: enzyme]] | [[Category: enzyme]] | ||
| Line 25: | Line 25: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:01:24 2008'' |
Revision as of 16:01, 21 February 2008
|
QPRTASE STRUCTURE FROM HUMAN
Overview
Human quinolinate phosphoribosyltransferase (EC 2.4.2.19) (hQPRTase) is a member of the type II phosphoribosyltransferase family involved in the catabolism of quinolinic acid (QA). It catalyses the formation of nicotinic acid mononucleotide from quinolinic acid, which involves a phosphoribosyl transfer reaction followed by decarboxylation. hQPRTase has been implicated in a number of neurological conditions and in order to study it further, we have carried out structural and kinetic studies on recombinant hQPRTase. The structure of the fully active enzyme overexpressed in Escherichia coli was solved using multiwavelength methods to a resolution of 2.0 A. hQPRTase has a alpha/beta barrel fold sharing a similar overall structure with the bacterial QPRTases. The active site of hQPRTase is located at an alpha/beta open sandwich structure that serves as a cup for the alpha/beta barrel of the adjacent subunit with a QA binding site consisting of three arginine residues (R102, R138 and R161) and two lysine residues (K139 and K171). Mutation of these residues affected substrate binding or abolished the enzymatic activity. The kinetics of the human enzyme are different to the bacterial enzymes studied, hQPRTase is inhibited competitively and non-competitively by one of its substrates, 5-phosphoribosylpyrophosphate (PRPP). The human enzyme adopts a hexameric arrangement, which places the active sites in close proximity to each other.
About this Structure
2JBM is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Nicotinate-nucleotide diphosphorylase (carboxylating), with EC number 2.4.2.19 Known structural/functional Sites: , , , , , , , , , , and . Full crystallographic information is available from OCA.
Reference
Structural and kinetic characterization of quinolinate phosphoribosyltransferase (hQPRTase) from homo sapiens., Liu H, Woznica K, Catton G, Crawford A, Botting N, Naismith JH, J Mol Biol. 2007 Oct 26;373(3):755-63. Epub 2007 Aug 24. PMID:17868694
Page seeded by OCA on Thu Feb 21 18:01:24 2008
