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[[Image:1w30.gif|left|200px]]
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{{STRUCTURE_1w30|  PDB=1w30  |  SCENE=  }}
'''PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET'''


==PyrR of Mycobacterium Tuberculosis as a potential drug target==
<StructureSection load='1w30' size='340' side='right'caption='[[1w30]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1w30]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W30 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w30 OCA], [https://pdbe.org/1w30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w30 RCSB], [https://www.ebi.ac.uk/pdbsum/1w30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w30 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PYRR_MYCTU PYRR_MYCTU] Regulates the transcription of the pyrimidine nucleotide (pyr) operon in response to exogenous pyrimidines (By similarity).  Also displays a weak uracil phosphoribosyltransferase activity which is not physiologically significant (By similarity).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w3/1w30_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1w30 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Overview==
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<ref>PMID:15805589</ref>
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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1W30 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W30 OCA].
</div>
<div class="pdbe-citations 1w30" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/15805589 15805589]
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Single protein]]
[[Category: Castro P]]
[[Category: Uracil phosphoribosyltransferase]]
[[Category: Kantardjieff KA]]
[[Category: Castro, P.]]
[[Category: Kim C-Y]]
[[Category: Kantardjieff, K A.]]
[[Category: Lekin T]]
[[Category: Kim, C Y.]]
[[Category: Rho B-S]]
[[Category: Lekin, T.]]
[[Category: Rupp B]]
[[Category: Rho, B S.]]
[[Category: Segelke BW]]
[[Category: Rupp, B.]]
[[Category: Terwilliger T]]
[[Category: Segelke, B W.]]
[[Category: Vasquez C]]
[[Category: TBSGC, TB Structural Genomics Consortium.]]
[[Category: Warfel NN]]
[[Category: Terwilliger, T.]]
[[Category: Vasquez, C.]]
[[Category: Warfel, N N.]]
[[Category: Protein structure initiative]]
[[Category: Psi]]
[[Category: Pyrr,transferase,glycosyltransferase,psi,protein structure initiative,tb structural genomics consortium,tb]]
[[Category: Tbsgc]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 13:05:04 2008''

Latest revision as of 13:13, 13 December 2023

PyrR of Mycobacterium Tuberculosis as a potential drug target

1w30, resolution 1.90Å

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