1ula
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Competitive inhibitors of the salvage pathway enzyme purine-nucleoside | + | Competitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ULA 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=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 1ULA 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=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 2PNP. Active as [http://en.wikipedia.org/wiki/Purine-nucleoside_phosphorylase Purine-nucleoside phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.1 2.4.2.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ULA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Purine-nucleoside phosphorylase]] | [[Category: Purine-nucleoside phosphorylase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Babu, Y | + | [[Category: Babu, Y S.]] |
| - | [[Category: Bugg, C | + | [[Category: Bugg, C E.]] |
| - | [[Category: Carter, D | + | [[Category: Carter, D C.]] |
| - | [[Category: Chen, S | + | [[Category: Chen, S F.]] |
| - | [[Category: Cook, W | + | [[Category: Cook, W J.]] |
| - | [[Category: Ealick, S | + | [[Category: Ealick, S E.]] |
| - | [[Category: Greenhough, T | + | [[Category: Greenhough, T J.]] |
[[Category: Habash, J.]] | [[Category: Habash, J.]] | ||
| - | [[Category: Helliwell, J | + | [[Category: Helliwell, J R.]] |
| - | [[Category: Parksjunior, R | + | [[Category: Parksjunior, R E.]] |
| - | [[Category: Rule, S | + | [[Category: Rule, S A.]] |
| - | [[Category: Stoeckler, J | + | [[Category: Stoeckler, J D.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: pentosyltransferase]] | [[Category: pentosyltransferase]] | ||
| - | ''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 15:25:43 2008'' |
Revision as of 13:25, 21 February 2008
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APPLICATION OF CRYSTALLOGRAPHIC AND MODELING METHODS IN THE DESIGN OF PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS
Contents |
Overview
Competitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported.
Disease
Known diseases associated with this structure: Neutral lipid storage disease with myopathy OMIM:[609059], Nucleoside phosphorylase deficiency, immunodeficiency due to OMIM:[164050]
About this Structure
1ULA is a Single protein structure of sequence from Homo sapiens with as ligand. This structure supersedes the now removed PDB entry 2PNP. Active as Purine-nucleoside phosphorylase, with EC number 2.4.2.1 Full crystallographic information is available from OCA.
Reference
Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors., Ealick SE, Babu YS, Bugg CE, Erion MD, Guida WC, Montgomery JA, Secrist JA 3rd, Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11540-4. PMID:1763067
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