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| - | [[Image:1qpr.gif|left|200px]] | |
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| - | {{Structure
| + | ==QUINOLINATE PHOSPHORIBOSYLTRANSFERASE (QAPRTASE) FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH PHTHALATE AND PRPCP== |
| - | |PDB= 1qpr |SIZE=350|CAPTION= <scene name='initialview01'>1qpr</scene>, resolution 2.45Å
| + | <StructureSection load='1qpr' size='340' side='right'caption='[[1qpr]], [[Resolution|resolution]] 2.45Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PHT:PHTHALIC+ACID'>PHT</scene>, <scene name='pdbligand=PPC:5-PHOSPHORIBOSYL-1-(BETA-METHYLENE)+PYROPHOSPHATE'>PPC</scene> | + | <table><tr><td colspan='2'>[[1qpr]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QPR FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinate-nucleotide_diphosphorylase_(carboxylating) Nicotinate-nucleotide diphosphorylase (carboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.19 2.4.2.19] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> |
| - | |GENE= NADC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PHT:PHTHALIC+ACID'>PHT</scene>, <scene name='pdbligand=PPC:5-PHOSPHORIBOSYL-1-(BETA-METHYLENE)+PYROPHOSPHATE'>PPC</scene></td></tr> |
| - | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=cd01572 QPRTase], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=PRK07896 PRK07896]</span>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1qpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qpr OCA], [https://pdbe.org/1qpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qpr RCSB], [https://www.ebi.ac.uk/pdbsum/1qpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qpr ProSAT], [https://www.topsan.org/Proteins/TBSGC/1qpr TOPSAN]</span></td></tr> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qpr OCA], [http://www.ebi.ac.uk/pdbsum/1qpr PDBsum], [http://www.fli-leibniz.de/cgi-bin/ImgLib.pl?CODE=1kfv JenaLib], [http://www.rcsb.org/pdb/explore.do?structureId=1qpr RCSB]</span>
| + | </table> |
| - | }}
| + | == Function == |
| | + | [https://www.uniprot.org/uniprot/NADC_MYCTU NADC_MYCTU] Involved in the catabolism of quinolinic acid (QA) (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/qp/1qpr_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=1qpr ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''QUINOLINATE PHOSPHORIBOSYLTRANSFERASE (QAPRTASE) FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH PHTHALATE AND PRPCP'''
| + | ==See Also== |
| - | | + | *[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview==
| + | </StructureSection> |
| - | Background:. Mycobacterium tuberculosis is the single most deadly human pathogen and is responsible for nearly three million deaths every year. Recent elucidation of the mode of action of isoniazid, a frontline antimycobacterial drug, suggests that NAD metabolism is extremely critical for this microorganism. M. tuberculosis depends solely on the de novo pathway to meet its NAD demand. Quinolinic acid phosphoribosyltransferase (QAPRTase), a key enzyme in the de novo biosynthesis of NAD, provides an attractive target for designing novel antitubercular drugs. Results:. The X-ray crystal structure of the M. tuberculosis QAPRTase apoenzyme has been determined by multiple isomorphous replacement at 2.4 A resolution. Structures of the enzyme have also been solved in complex with the substrate quinolinic acid (QA), the inhibitory QA analog phthalic acid (PA), the product nicotinate mononucleotide (NAMN), and as a ternary complex with PA and a substrate analog, 5-phosphoribosyl-1-(beta-methylene)pyrophosphate (PRPCP). The structure of the nonproductive QAPRTase-PA-PRPCP Michaelis complex reveals a 5-phosphoribosyl-1-pyrophosphate-binding site that is different from the one observed in type I phosphoribosyltransferases (PRTases). The type II PRTase active site of QAPRTase undergoes conformational changes that appear to be important in determining substrate specificity and eliciting productive catalysis. Conclusions:. QAPRTase is the only known representative of the type II PRTase fold, an unusual alpha/beta barrel, and appears to represent convergent evolution for PRTase catalysis. The active site of type II PRTase bears little resemblance to the better known type I enzymes.
| + | [[Category: Large Structures]] |
| - | | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | ==About this Structure== | + | [[Category: Grubmeyer C]] |
| - | 1QPR 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=1QPR OCA].
| + | [[Category: Sacchettini JC]] |
| - | | + | [[Category: Sharma V]] |
| - | ==Reference==
| + | |
| - | Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target., Sharma V, Grubmeyer C, Sacchettini JC, Structure. 1998 Dec 15;6(12):1587-99. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9862811 9862811]
| + | |
| - | [[Category: Mycobacterium tuberculosis]] | + | |
| - | [[Category: Nicotinate-nucleotide diphosphorylase (carboxylating)]] | + | |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Grubmeyer, C.]] | + | |
| - | [[Category: Sacchettini, J C.]] | + | |
| - | [[Category: Sharma, V.]] | + | |
| - | [[Category: TBSGC, TB Structural Genomics Consortium.]]
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| - | [[Category: de novo nad biosynthesis]]
| + | |
| - | [[Category: phosphoribosyltransferase]]
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| - | [[Category: protein structure initiative]]
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| - | [[Category: prpp]]
| + | |
| - | [[Category: prtase]]
| + | |
| - | [[Category: psi]]
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| - | [[Category: quinolinic acid]]
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| - | [[Category: structural genomic]]
| + | |
| - | [[Category: tb structural genomics consortium]]
| + | |
| - | [[Category: tbsgc]]
| + | |
| - | [[Category: transferase]]
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 26 06:02:08 2008''
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