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1n2i

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(New page: 200px<br /><applet load="1n2i" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n2i, resolution 1.70&Aring;" /> '''Crystal Structure of...)
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[[Image:1n2i.gif|left|200px]]<br /><applet load="1n2i" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1n2i, resolution 1.70&Aring;" />
 
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'''Crystal Structure of Pantothenate Synthetase from M. tuberculosis in complex with a reaction intermediate, pantoyl adenylate, different occupancies of pantoyl adenylate'''<br />
 
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==Overview==
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==Crystal Structure of Pantothenate Synthetase from M. tuberculosis in complex with a reaction intermediate, pantoyl adenylate, different occupancies of pantoyl adenylate==
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Pantothenate biosynthesis is essential for the virulence of Mycobacterium, tuberculosis, and this pathway thus presents potential drug targets, against tuberculosis. We determined the crystal structure of pantothenate, synthetase (PS) from M. tuberculosis, and its complexes with AMPCPP, pantoate, and a reaction intermediate, pantoyl adenylate, with resolutions, from 1.6 to 2 A. PS catalyzes the ATP-dependent condensation of pantoate, and beta-alanine to form pantothenate. Its structure reveals a dimer, and, each subunit has two domains with tight association between domains. The, active-site cavity is on the N-terminal domain, partially covered by the, C-terminal domain. One wall of the active site cavity is flexible, which, allows the bulky AMPCPP to diffuse into the active site to nearly full, occupancy when crystals are soaked in solutions containing AMPCPP. Crystal, structures of the complexes with AMPCPP and pantoate indicate that the, enzyme binds ATP and pantoate tightly in the active site, and brings the, carboxyl oxygen of pantoate near the alpha-phosphorus atom of ATP for an, in-line nucleophilic attack. When crystals were soaked with, or grown in, the presence of, both ATP and pantoate, a reaction intermediate, pantoyl, adenylate, is found in the active site. The flexible wall of the active, site cavity becomes ordered when the intermediate is in the active site, thus protecting it from being hydrolyzed. Binding of beta-alanine can, occur only after pantoyl adenylate is formed inside the active site, cavity. The tight binding of the intermediate pantoyl adenylate suggests, that nonreactive analogs of pantoyl adenylate may be inhibitors of the PS, enzyme with high affinity and specificity.
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<StructureSection load='1n2i' size='340' side='right'caption='[[1n2i]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1n2i]] 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=1N2I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N2I FirstGlance]. <br>
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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]] 1.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PAJ:PANTOYL+ADENYLATE'>PAJ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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=1n2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n2i OCA], [https://pdbe.org/1n2i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n2i RCSB], [https://www.ebi.ac.uk/pdbsum/1n2i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n2i ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PANC_MYCTU PANC_MYCTU] Catalyzes the condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.<ref>PMID:11669627</ref>
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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/n2/1n2i_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=1n2i ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1N2I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with SO4, PAJ, GOL and EOH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pantoate--beta-alanine_ligase Pantoate--beta-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.1 6.3.2.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N2I OCA].
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*[[Pantothenate synthetase|Pantothenate synthetase]]
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== References ==
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==Reference==
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<references/>
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Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate., Wang S, Eisenberg D, Protein Sci. 2003 May;12(5):1097-108. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12717031 12717031]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Pantoate--beta-alanine ligase]]
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[[Category: Eisenberg D]]
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[[Category: Single protein]]
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[[Category: Wang S]]
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[[Category: Eisenberg, D.]]
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[[Category: TBSGC, TB.Structural.Genomics.Consortium.]]
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[[Category: Wang, S.]]
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[[Category: EOH]]
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[[Category: GOL]]
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[[Category: PAJ]]
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[[Category: SO4]]
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[[Category: dimer]]
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[[Category: intersubunit beta sheet]]
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[[Category: protein structure initiative]]
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[[Category: psi]]
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[[Category: rossmann fold]]
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[[Category: structural genomics]]
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[[Category: tb structural genomics consortium]]
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[[Category: tbsgc]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:53:40 2007''
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Current revision

Crystal Structure of Pantothenate Synthetase from M. tuberculosis in complex with a reaction intermediate, pantoyl adenylate, different occupancies of pantoyl adenylate

PDB ID 1n2i

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