1qk5: Difference between revisions
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|PDB= 1qk5 |SIZE=350|CAPTION= <scene name='initialview01'>1qk5</scene>, resolution 1.60Å | |PDB= 1qk5 |SIZE=350|CAPTION= <scene name='initialview01'>1qk5</scene>, resolution 1.60Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=XMP:XANTHOSINE-5 | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=XMP:XANTHOSINE-5'-MONOPHOSPHATE'>XMP</scene> and <scene name='pdbligand=POP:PYROPHOSPHATE 2-'>POP</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= [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] | ||
|GENE= | |GENE= | ||
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[[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 Sun Mar 23 13:21:18 2008'' | ||
Revision as of 14:21, 23 March 2008
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| , resolution 1.60Å | |||||||
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| Ligands: | , and | ||||||
| Activity: | Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
TOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH XMP, PYROPHOSPHATE AND TWO MG2+ IONS
OverviewOverview
The crystal structure of the Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-xanthosine 5'-monophosphate (XMP)-pyrophosphate-Mg(2+) ternary complex has been determined at 1. 60 A resolution. This biproduct, post-transition state structure is of a T. gondii HGPRT mutant (Asp150Ala or D150A). The D150A mutant has reduced activity (k(cat) lower by 11-, 296-, and 8.6-fold for hypoxanthine, guanine, and xanthine, respectively) compared to wild-type T. gondii HGPRT. The Michaelis constants for purine bases are altered only slightly, whereas those for alpha-D-5-phosphoribosyl 1-pyrophosphate (PRPP) are lower by approximately 6.5-fold. The ternary complex crystallizes in space group C222(1) (a = 55.21 A, b = 112.25 A, and c = 144.28 A) with two subunits in the asymmetric unit; the HGPRT tetramer is completed by the application of 2-fold crystallographic symmetry. All active sites contain XMP inverted question markbound in a fashion similar to that of the guanosine 5'-monophosphate (GMP) and inosine 5'-monophosphate (IMP) complexes reported in the preceding article [Heroux, A., et al. (1999) Biochemistry 38, 14485-14494] inverted question mark, pyrophosphate, and two Mg(2+) ions. Each Mg(2+) ion is octahedrally coordinated by two terminal pyrophosphate oxygen atoms and several ordered water molecules. This structure shows how HGPRT uses two Mg(2+) ions to orient and activate the pyrophosphate moiety of PRPP for attack by a purine base, and why mutation in humans of the residue corresponding to Asp206, the only HGPRT amino acid that directly contacts the Mg(2+) ions, causes Lesch-Nyhan syndrome (HGPRT(Kinston), D193N). The Leu78-Lys79 peptide bond in the active site adopts the cis configuration, which it must to bind PRPP or pyrophosphate. The contribution of cis-trans isomerization of this peptide bond to the energetics of substrate binding and product release is discussed. A comprehensive description of the HGPRT reaction mechanism is also proposed.
About this StructureAbout this Structure
1QK5 is a Single protein structure of sequence from Toxoplasma gondii. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase with XMP, pyrophosphate, and two Mg(2+) ions bound: insights into the catalytic mechanism., Heroux A, White EL, Ross LJ, Davis RL, Borhani DW, Biochemistry. 1999 Nov 2;38(44):14495-506. PMID:10545171
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