2i3a

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[[Image:2i3a.gif|left|200px]]<br /><applet load="2i3a" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2i3a, resolution 2.15&Aring;" />
 
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'''Crystal structure of N-Acetyl-gamma-Glutamyl-Phosphate Reductase (Rv1652) from Mycobacterium tuberculosis'''<br />
 
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==Overview==
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==Crystal structure of N-Acetyl-gamma-Glutamyl-Phosphate Reductase (Rv1652) from Mycobacterium tuberculosis==
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The enzyme N-acetyl-gamma-glutamyl-phosphate reductase (AGPR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductive dephosphorylation of N-acetyl-gamma-glutamyl-phosphate to N-acetylglutamate-gamma-semialdehyde. This reaction is part of the arginine biosynthetic pathway that is essential for some microorganisms and plants, in particular, for Mycobacterium tuberculosis (Mtb). The structures of apo MtbAGPR in the space groups P2(1)2(1)2(1) and C2 and the structure of MtbAGPR bound to the cofactor NADP(+) have been solved and analyzed. Each MtbAGPR subunit consists of alpha/beta and alpha+beta domains; NADP(+) is bound in the cleft between them. The hydrogen bonds and hydrophobic contacts between the enzyme and cofactor have been examined. Comparison of the apo and the bound enzyme structures has revealed a conformational change in MtbAGPR upon NADP(+) binding. Namely, a loop (Leu88 to His92) moves more than 5 A to confine sterically the cofactor's adenine moiety in a hydrophobic pocket. To identify the catalytically important residues in MtbAGPR, a docking of the substrate to the enzyme has been performed using the present structure of the MtbAGPR/NADP(+) complex. It reveals that residues His217 and His219 could form hydrogen bonds with the docked substrate. In addition, an ion pair could form between the substrate phosphate group and the guanidinium group of Arg114. These interactions optimally place and orient the substrate for subsequent nucleophilic attack by Cys158 on the substrate gamma-carboxyl group. His219 is the most probable general base to accept a proton from Cys158 and an adjacent ion pair interaction with the side-chain carboxyl group of Glu222 could help to stabilize the resulting positive charge on His219. For this catalytic triad to function efficiently it requires a small conformational change of the order of 1 A in the loop containing His217 and His219; this could easily result from the substrate binding.
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<StructureSection load='2i3a' size='340' side='right'caption='[[2i3a]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2i3a]] is a 4 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=2I3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I3A FirstGlance]. <br>
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2I3A 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=BTB:'>BTB</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/N-acetyl-gamma-glutamyl-phosphate_reductase N-acetyl-gamma-glutamyl-phosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.38 1.2.1.38] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I3A OCA].
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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]] 2.15&#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=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene></td></tr>
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==Reference==
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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=2i3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i3a OCA], [https://pdbe.org/2i3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i3a RCSB], [https://www.ebi.ac.uk/pdbsum/2i3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i3a ProSAT]</span></td></tr>
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Crystal structure of N-acetyl-gamma-glutamyl-phosphate reductase from Mycobacterium tuberculosis in complex with NADP(+)., Cherney LT, Cherney MM, Garen CR, Niu C, Moradian F, James MN, J Mol Biol. 2007 Apr 13;367(5):1357-69. Epub 2007 Jan 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17316682 17316682]
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</table>
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[[Category: Mycobacterium tuberculosis]]
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== Function ==
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[[Category: N-acetyl-gamma-glutamyl-phosphate reductase]]
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[https://www.uniprot.org/uniprot/ARGC_MYCTU ARGC_MYCTU]
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[[Category: Single protein]]
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== Evolutionary Conservation ==
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[[Category: Cherney, L T.]]
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[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Cherney, M M.]]
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Check<jmol>
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[[Category: Garen, C R.]]
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<jmolCheckbox>
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[[Category: James, M N.G.]]
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i3/2i3a_consurf.spt"</scriptWhenChecked>
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[[Category: Moraidin, F.]]
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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[[Category: XMTB, Mycobacterium Tuberculosis Structural Proteomics Project.]]
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<text>to colour the structure by Evolutionary Conservation</text>
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[[Category: BTB]]
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</jmolCheckbox>
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[[Category: dimer interface beta sandwich]]
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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=2i3a ConSurf].
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[[Category: mycobacterium tuberculosis structural proteomics project]]
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<div style="clear:both"></div>
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[[Category: rossmann fold]]
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__TOC__
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[[Category: structural genomics]]
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</StructureSection>
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[[Category: tetramer]]
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[[Category: Large Structures]]
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[[Category: xmtb]]
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[[Category: Mycobacterium tuberculosis H37Rv]]
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[[Category: Cherney LT]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:48:36 2008''
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[[Category: Cherney MM]]
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[[Category: Garen CR]]
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[[Category: James MNG]]
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[[Category: Moraidin F]]

Current revision

Crystal structure of N-Acetyl-gamma-Glutamyl-Phosphate Reductase (Rv1652) from Mycobacterium tuberculosis

PDB ID 2i3a

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