1w30
From Proteopedia
(New page: 200px<br /><applet load="1w30" size="450" color="white" frame="true" align="right" spinBox="true" caption="1w30, resolution 1.90Å" /> '''PYRR OF MYCOBACTERIU...) |
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| - | [[Image:1w30.gif|left|200px]]<br /><applet load="1w30" size=" | + | [[Image:1w30.gif|left|200px]]<br /><applet load="1w30" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1w30, resolution 1.90Å" /> | caption="1w30, resolution 1.90Å" /> | ||
'''PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET'''<br /> | '''PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Mycobacterium tuberculosis pyrR gene (Rv1379) encodes a protein that | + | The Mycobacterium tuberculosis pyrR gene (Rv1379) encodes a protein that regulates the expression of pyrimidine-nucleotide biosynthesis (pyr) genes in a UMP-dependent manner. Because pyrimidine biosynthesis is an essential step in the progression of TB, the gene product pyrR is an attractive antitubercular drug target. The 1.9 A native structure of Mtb pyrR determined by the TB Structural Genomics Consortium facilities in trigonal space group P3(1)21 is reported, with unit-cell parameters a = 66.64, c = 154.72 A at 120 K and two molecules in the asymmetric unit. The three-dimensional structure and residual uracil phosphoribosyltransferase activity point to a common PRTase ancestor for pyrR. However, while PRPP- and UMP-binding sites have been retained in Mtb pyrR, a distinct dimer interaction among subunits creates a deep positively charged cleft capable of binding pyr mRNA. In silico screening of pyrimidine-nucleoside analogs has revealed a number of potential lead compounds that, if bound to Mtb pyrR, could facilitate transcriptional attenuation, particularly cyclopentenyl nucleosides. |
==About this Structure== | ==About this Structure== | ||
| - | 1W30 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Active as [http://en.wikipedia.org/wiki/Uracil_phosphoribosyltransferase Uracil phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.9 2.4.2.9] Full crystallographic information is available from [http:// | + | 1W30 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Active as [http://en.wikipedia.org/wiki/Uracil_phosphoribosyltransferase Uracil phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.9 2.4.2.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W30 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Uracil phosphoribosyltransferase]] | [[Category: Uracil phosphoribosyltransferase]] | ||
[[Category: Castro, P.]] | [[Category: Castro, P.]] | ||
| - | [[Category: Kantardjieff, K | + | [[Category: Kantardjieff, K A.]] |
| - | [[Category: Kim, C | + | [[Category: Kim, C Y.]] |
[[Category: Lekin, T.]] | [[Category: Lekin, T.]] | ||
| - | [[Category: Rho, B | + | [[Category: Rho, B S.]] |
[[Category: Rupp, B.]] | [[Category: Rupp, B.]] | ||
| - | [[Category: Segelke, B | + | [[Category: Segelke, B W.]] |
| - | [[Category: TBSGC, TB | + | [[Category: TBSGC, TB Structural Genomics Consortium.]] |
[[Category: Terwilliger, T.]] | [[Category: Terwilliger, T.]] | ||
[[Category: Vasquez, C.]] | [[Category: Vasquez, C.]] | ||
| - | [[Category: Warfel, N | + | [[Category: Warfel, N N.]] |
[[Category: glycosyltransferase]] | [[Category: glycosyltransferase]] | ||
[[Category: protein structure initiative]] | [[Category: protein structure initiative]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:39:54 2008'' |
Revision as of 13:39, 21 February 2008
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PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET
Overview
The Mycobacterium tuberculosis pyrR gene (Rv1379) encodes a protein that regulates the expression of pyrimidine-nucleotide biosynthesis (pyr) genes in a UMP-dependent manner. Because pyrimidine biosynthesis is an essential step in the progression of TB, the gene product pyrR is an attractive antitubercular drug target. The 1.9 A native structure of Mtb pyrR determined by the TB Structural Genomics Consortium facilities in trigonal space group P3(1)21 is reported, with unit-cell parameters a = 66.64, c = 154.72 A at 120 K and two molecules in the asymmetric unit. The three-dimensional structure and residual uracil phosphoribosyltransferase activity point to a common PRTase ancestor for pyrR. However, while PRPP- and UMP-binding sites have been retained in Mtb pyrR, a distinct dimer interaction among subunits creates a deep positively charged cleft capable of binding pyr mRNA. In silico screening of pyrimidine-nucleoside analogs has revealed a number of potential lead compounds that, if bound to Mtb pyrR, could facilitate transcriptional attenuation, particularly cyclopentenyl nucleosides.
About this Structure
1W30 is a Single protein structure of sequence from Mycobacterium tuberculosis. Active as Uracil phosphoribosyltransferase, with EC number 2.4.2.9 Full crystallographic information is available from OCA.
Reference
Structure of pyrR (Rv1379) from Mycobacterium tuberculosis: a persistence gene and protein drug target., Kantardjieff KA, Vasquez C, Castro P, Warfel NM, Rho BS, Lekin T, Kim CY, Segelke BW, Terwilliger TC, Rupp B, Acta Crystallogr D Biol Crystallogr. 2005 Apr;61(Pt 4):355-64. Epub 2005, Mar 24. PMID:15805589
Page seeded by OCA on Thu Feb 21 15:39:54 2008
Categories: Mycobacterium tuberculosis | Single protein | Uracil phosphoribosyltransferase | Castro, P. | Kantardjieff, K A. | Kim, C Y. | Lekin, T. | Rho, B S. | Rupp, B. | Segelke, B W. | TBSGC, TB Structural Genomics Consortium. | Terwilliger, T. | Vasquez, C. | Warfel, N N. | Glycosyltransferase | Protein structure initiative | Psi | Pyrr | Tb | Tb structural genomics consortium | Tbsgc | Transferase
