1yfz
From Proteopedia
(New page: 200px<br /><applet load="1yfz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yfz, resolution 2.20Å" /> '''Novel IMP Binding in...) |
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| - | [[Image:1yfz.gif|left|200px]]<br /><applet load="1yfz" size=" | + | [[Image:1yfz.gif|left|200px]]<br /><applet load="1yfz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1yfz, resolution 2.20Å" /> | caption="1yfz, resolution 2.20Å" /> | ||
'''Novel IMP Binding in Feedback Inhibition of Hypoxanthine-Guanine Phosphoribosyltransferase from Thermoanaerobacter tengcongensis'''<br /> | '''Novel IMP Binding in Feedback Inhibition of Hypoxanthine-Guanine Phosphoribosyltransferase from Thermoanaerobacter tengcongensis'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Crystal structures of Thermoanaerobacter tengcongensis | + | Crystal structures of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) apoenzyme and the enzyme-inosine monophosphate (IMP) complex have been determined to 2.5A and 2.2A resolution, respectively. The active form of the enzyme was identified as a tetramer in solution and the K(i) value of IMP was measured to be 45 microM for alpha-D-phosphoribosyl-1-pyrophosphate (PRPP). Conformation of the flexible loop in T.tengcongensis HGPRT, which is involved in substrate PRPP binding, is different from that observed in phosphoribosyltransferases (PRTs). It contains a 3-10 helix, and a unique double serine repeat. This loop is ordered even in the apoenzyme and assumes a half-closed conformation. The primary magnesium ion is directly coordinated by side-chains of Glu101 and Asp102, and water molecules in the apoenzyme, suggesting a possible prerequisite role for substrate PRPP binding. Most interestingly, an alternative IMP binding mode is found in the structure of T.tengcongensis HGPRT-IMP complex. The 5'-phosphate of IMP occupies the PPi position usually seen in PRT-PRPP complexes. This new observation is consistent with the lower K(i) value of IMP and may suggest a mechanism involving multiple modes of interactions between IMP and T.tengcongensis HGPRT in product release and feedback inhibition. The structure of T.tengcongensis HGPRT is compared with those of mesophilic HPRTs, and several possible features contributing to its thermostability are elucidated. Overall, T.tengcongensis HGPRT appears to be more diverged from other PRTs. |
==About this Structure== | ==About this Structure== | ||
| - | 1YFZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermoanaerobacter_tengcongensis Thermoanaerobacter tengcongensis] with ACT, MG and IMP 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:// | + | 1YFZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermoanaerobacter_tengcongensis Thermoanaerobacter tengcongensis] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=IMP:'>IMP</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=1YFZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-nucleotide complex]] | [[Category: protein-nucleotide complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:04:56 2008'' |
Revision as of 14:05, 21 February 2008
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Novel IMP Binding in Feedback Inhibition of Hypoxanthine-Guanine Phosphoribosyltransferase from Thermoanaerobacter tengcongensis
Overview
Crystal structures of Thermoanaerobacter tengcongensis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) apoenzyme and the enzyme-inosine monophosphate (IMP) complex have been determined to 2.5A and 2.2A resolution, respectively. The active form of the enzyme was identified as a tetramer in solution and the K(i) value of IMP was measured to be 45 microM for alpha-D-phosphoribosyl-1-pyrophosphate (PRPP). Conformation of the flexible loop in T.tengcongensis HGPRT, which is involved in substrate PRPP binding, is different from that observed in phosphoribosyltransferases (PRTs). It contains a 3-10 helix, and a unique double serine repeat. This loop is ordered even in the apoenzyme and assumes a half-closed conformation. The primary magnesium ion is directly coordinated by side-chains of Glu101 and Asp102, and water molecules in the apoenzyme, suggesting a possible prerequisite role for substrate PRPP binding. Most interestingly, an alternative IMP binding mode is found in the structure of T.tengcongensis HGPRT-IMP complex. The 5'-phosphate of IMP occupies the PPi position usually seen in PRT-PRPP complexes. This new observation is consistent with the lower K(i) value of IMP and may suggest a mechanism involving multiple modes of interactions between IMP and T.tengcongensis HGPRT in product release and feedback inhibition. The structure of T.tengcongensis HGPRT is compared with those of mesophilic HPRTs, and several possible features contributing to its thermostability are elucidated. Overall, T.tengcongensis HGPRT appears to be more diverged from other PRTs.
About this Structure
1YFZ is a Single protein structure of sequence from Thermoanaerobacter tengcongensis with , and as ligands. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Full crystallographic information is available from OCA.
Reference
Alternative IMP binding in feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis., Chen Q, Liang Y, Su X, Gu X, Zheng X, Luo M, J Mol Biol. 2005 May 20;348(5):1199-210. Epub 2005 Apr 7. PMID:15854655
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