2gvw

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[[Image:2gvw.jpg|left|200px]]<br /><applet load="2gvw" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2gvw, resolution 1.86&Aring;" />
 
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'''Structure of diisopropyl fluorophosphatase (DFPase) holoenzyme (RT)'''<br />
 
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==Overview==
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==Structure of diisopropyl fluorophosphatase (DFPase) holoenzyme (RT)==
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A wide range of organophosphorus nerve agents, including Soman, Sarin, and Tabun is efficiently hydrolyzed by the phosphotriesterase enzyme diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris. To date, the lack of available inhibitors of DFPase has limited studies on its mechanism. The de novo design, synthesis, and characterization of substrate analogues acting as competitive inhibitors of DFPase are reported. The 1.73 A crystal structure of O,O-dicyclopentylphosphoroamidate (DcPPA) bound to DFPase shows a direct coordination of the phosphoryl oxygen by the catalytic calcium ion. The binding mode of this substrate analogue suggests a crucial role for electrostatics in the orientation of the ligand in the active site. This interpretation is further supported by the crystal structures of double mutants D229N/N120D and D229N/N175D, designed to reorient the electrostatic environment around the catalytic calcium. The structures show no differences in their calcium coordinating environment, although they are enzymatically inactive. Additional double mutants E21Q/N120D and E21Q/N175D are also inactive. On the basis of these crystal structures and kinetic and mutagenesis data as well as isotope labeling we propose a new mechanism for DFPase activity. Calcium coordinating residue D229, in concert with direct substrate activation by the metal ion, renders the phosphorus atom of the substrate susceptible for attack of water, through generation of a phosphoenzyme intermediate. Our proposed mechanism may be applicable to the structurally related enzyme paraoxonase (PON), a component of high-density lipoprotein (HDL).
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<StructureSection load='2gvw' size='340' side='right'caption='[[2gvw]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2gvw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Loligo_vulgaris Loligo vulgaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GVW 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]] 1.86&#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=CA:CALCIUM+ION'>CA</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=2gvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvw OCA], [https://pdbe.org/2gvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gvw RCSB], [https://www.ebi.ac.uk/pdbsum/2gvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gvw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DFPA_LOLVU DFPA_LOLVU] Biological function and substrate unknown. However, it is capable of acting on phosphorus anhydride bonds (such as phosphorus-halide and phosphorus-cyanide) in organophosphorus compounds (including nerve gases).<ref>PMID:15966726</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/gv/2gvw_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=2gvw 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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2GVW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Loligo_vulgaris Loligo vulgaris] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Diisopropyl-fluorophosphatase Diisopropyl-fluorophosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.8.2 3.1.8.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVW OCA].
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*[[Phosphotriesterase 3D structures|Phosphotriesterase 3D structures]]
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== References ==
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==Reference==
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<references/>
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Binding of a designed substrate analogue to diisopropyl fluorophosphatase: implications for the phosphotriesterase mechanism., Blum MM, Lohr F, Richardt A, Ruterjans H, Chen JC, J Am Chem Soc. 2006 Oct 4;128(39):12750-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17002369 17002369]
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__TOC__
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[[Category: Diisopropyl-fluorophosphatase]]
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Loligo vulgaris]]
[[Category: Loligo vulgaris]]
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[[Category: Single protein]]
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[[Category: Blum MM]]
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[[Category: Blum, M M.]]
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[[Category: Chen JCH]]
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[[Category: Chen, J C.H.]]
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[[Category: CA]]
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[[Category: beta-propeller]]
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[[Category: phosphotriesterase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:35:57 2008''
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Current revision

Structure of diisopropyl fluorophosphatase (DFPase) holoenzyme (RT)

PDB ID 2gvw

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