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1w30

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[[Image:1w30.gif|left|200px]]
 
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{{Structure
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==PyrR of Mycobacterium Tuberculosis as a potential drug target==
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|PDB= 1w30 |SIZE=350|CAPTION= <scene name='initialview01'>1w30</scene>, resolution 1.90&Aring;
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<StructureSection load='1w30' size='340' side='right'caption='[[1w30]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<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>
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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</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>
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|GENE=
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<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>
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|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG2065 PyrR]</span>
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w30 OCA], [http://www.ebi.ac.uk/pdbsum/1w30 PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=1w30 RCSB]</span>
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== Function ==
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}}
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[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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w3/1w30_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''PYRR OF MYCOBACTERIUM TUBERCULOSIS AS A POTENTIAL DRUG TARGET'''
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1w30" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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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].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Large Structures]]
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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]
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[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Single protein]]
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[[Category: Castro P]]
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[[Category: Uracil phosphoribosyltransferase]]
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[[Category: Kantardjieff KA]]
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[[Category: Castro, P.]]
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[[Category: Kim C-Y]]
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[[Category: Kantardjieff, K A.]]
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[[Category: Lekin T]]
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[[Category: Kim, C Y.]]
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[[Category: Rho B-S]]
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[[Category: Lekin, T.]]
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[[Category: Rupp B]]
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[[Category: Rho, B S.]]
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[[Category: Segelke BW]]
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[[Category: Rupp, B.]]
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[[Category: Terwilliger T]]
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[[Category: Segelke, B W.]]
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[[Category: Vasquez C]]
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[[Category: TBSGC, TB Structural Genomics Consortium.]]
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[[Category: Warfel NN]]
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[[Category: Terwilliger, T.]]
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[[Category: Vasquez, C.]]
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[[Category: Warfel, N N.]]
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[[Category: protein structure initiative]]
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[[Category: psi]]
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[[Category: pyrr,transferase,glycosyltransferase,psi,protein structure initiative,tb structural genomics consortium,tb]]
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[[Category: tbsgc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 06:10:15 2008''
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Current revision

PyrR of Mycobacterium Tuberculosis as a potential drug target

PDB ID 1w30

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