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1n2g

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[[Image:1n2g.gif|left|200px]]<br /><applet load="1n2g" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1n2g, resolution 1.80&Aring;" />
 
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'''Crystal Structure of a Pantothenate Synthetase from M. tuberculosis in complex with AMPCPP'''<br />
 
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==Overview==
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==Crystal Structure of a Pantothenate Synthetase from M. tuberculosis in complex with AMPCPP==
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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='1n2g' size='340' side='right'caption='[[1n2g]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1n2g]] 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=1N2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N2G 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]] 1.8&#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=APC:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENOSYL+ESTER'>APC</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1n2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n2g OCA], [https://pdbe.org/1n2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n2g RCSB], [https://www.ebi.ac.uk/pdbsum/1n2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n2g 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/n2/1n2g_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=1n2g 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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1N2G 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 <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=APC:'>APC</scene>, <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=EOH:'>EOH</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1N2G 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: APC]]
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[[Category: EOH]]
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[[Category: GOL]]
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[[Category: MG]]
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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://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:01:36 2008''
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Current revision

Crystal Structure of a Pantothenate Synthetase from M. tuberculosis in complex with AMPCPP

PDB ID 1n2g

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