1d6n: Difference between revisions
New page: left|200px<br /> <applet load="1d6n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d6n, resolution 2.70Å" /> '''TERNARY COMPLEX STR... |
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'''TERNARY COMPLEX STRUCTURE OF HUMAN HGPRTASE, PRPP, MG2+, AND THE INHIBITOR HPP REVEALS THE INVOLVEMENT OF THE FLEXIBLE LOOP IN SUBSTRATE BINDING'''<br /> | '''TERNARY COMPLEX STRUCTURE OF HUMAN HGPRTASE, PRPP, MG2+, AND THE INHIBITOR HPP REVEALS THE INVOLVEMENT OF THE FLEXIBLE LOOP IN SUBSTRATE BINDING'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1D6N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, PPO and PRP as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | 1D6N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=PPO:'>PPO</scene> and <scene name='pdbligand=PRP:'>PRP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1D6N OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: hgprtase]] | [[Category: hgprtase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:38:48 2008'' | ||
Revision as of 16:38, 15 February 2008
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TERNARY COMPLEX STRUCTURE OF HUMAN HGPRTASE, PRPP, MG2+, AND THE INHIBITOR HPP REVEALS THE INVOLVEMENT OF THE FLEXIBLE LOOP IN SUBSTRATE BINDING
OverviewOverview
Site-directed mutagenesis was used to replace Lys68 of the human, hypoxanthine phosphoribosyltransferase (HGPRTase) with alanine to exploit, this less reactive form of the enzyme to gain additional insights into the, structure activity relationship of HGPRTase. Although this substitution, resulted in only a minimal (one- to threefold) increase in the Km values, for binding pyrophosphate or phosphoribosylpyrophosphate, the catalytic, efficiencies (k(cat)/Km) of the forward and reverse reactions were more, severely reduced (6- to 30-fold), and the mutant enzyme showed positive, cooperativity in binding of alpha-D-5-phosphoribosyl-1-pyrophosphate, (PRPP) and nucleotide. The K68A form of the human HGPRTase was, cocrystallized with 7-hydroxy [4,3-d] pyrazolo pyrimidine (HPP) and Mg, PRPP, and the refined structure reported. The PRPP molecule built into the, [(Fo - Fc)phi(calc)] electron density shows atomic interactions between, the Mg PRPP and enzyme residues in the pyrophosphate binding domain as, well as in a long flexible loop (residues Leu101 to Gly111) that closes, over the active site. Loop closure reveals the functional roles for the, conserved SY dipeptide of the loop as well as the molecular basis for one, form of gouty arthritis (S103R). In addition, the closed loop conformation, provides structural information relevant to the mechanism of catalysis in, human HGPRTase.
DiseaseDisease
Known diseases associated with this structure: HPRT-related gout OMIM:[308000], Lesch-Nyhan syndrome, 300322, OMIM:[308000]
About this StructureAbout this Structure
1D6N is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Full crystallographic information is available from OCA.
ReferenceReference
Ternary complex structure of human HGPRTase, PRPP, Mg2+, and the inhibitor HPP reveals the involvement of the flexible loop in substrate binding., Balendiran GK, Molina JA, Xu Y, Torres-Martinez J, Stevens R, Focia PJ, Eakin AE, Sacchettini JC, Craig SP 3rd, Protein Sci. 1999 May;8(5):1023-31. PMID:10338013
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