2gvx

<table><tr><td colspan='2'>[[2gvx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Common_european_squid Common european squid]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GVX FirstGlance]. <br>

</td></tr><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>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Diisopropyl-fluorophosphatase Diisopropyl-fluorophosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.8.2 3.1.8.2] </span></td></tr>

[[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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== Publication Abstract from PubMed ==

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).

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:17002369<ref>PMID:17002369</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 2gvx" style="background-color:#fffaf0;"></div>

[[Category: Common european squid]]

[[Category: Diisopropyl-fluorophosphatase]]

[[Category: Blum, M M]]

[[Category: Chen, J C.H]]

[[Category: Lohr, F]]

[[Category: Richardt, A]]

[[Category: Ruterjans, H]]

[[Category: Phosphotriesterase]]