1yhk

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

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(2E,6E)-farnesyl_diphosphate_synthase (2E,6E)-farnesyl diphosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.10 2.5.1.10] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yhk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yhk OCA], [http://pdbe.org/1yhk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yhk RCSB], [http://www.ebi.ac.uk/pdbsum/1yhk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yhk ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

Typanosoma cruzi, the causative agent of Chagas disease, has recently been shown to be sensitive to the action of the bisphosphonates currently used in bone resorption therapy. These compounds target the mevalonate pathway by inhibiting farnesyl diphosphate synthase (farnesyl pyrophosphate synthase, FPPS), the enzyme that condenses the diphosphates of C5 alcohols (isopentenyl and dimethylallyl) to form C10 and C15 diphosphates (geranyl and farnesyl). The structures of the T. cruzi FPPS (TcFPPS) alone and in two complexes with substrates and inhibitors reveal that following binding of the two substrates and three Mg2+ ions, the enzyme undergoes a conformational change consisting of a hinge-like closure of the binding site. In this conformation, it would be possible for the enzyme to bind a bisphosphonate inhibitor that spans the sites usually occupied by dimethylallyl diphosphate (DMAPP) and the homoallyl moiety of isopentenyl diphosphate. This observation may lead to the design of new, more potent anti-trypanosomal bisphosphonates, because existing FPPS inhibitors occupy only the DMAPP site. In addition, the structures provide an important mechanistic insight: after its formation, geranyl diphosphate can swing without leaving the enzyme, from the product site to the substrate site to participate in the synthesis of farnesyl diphosphate.

Structure and mechanism of the farnesyl diphosphate synthase from Trypanosoma cruzi: implications for drug design.,Gabelli SB, McLellan JS, Montalvetti A, Oldfield E, Docampo R, Amzel LM Proteins. 2006 Jan 1;62(1):80-8. PMID:16288456<ref>PMID:16288456</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 1yhk" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Trycr]]

[[Category: Amzel, L M]]

[[Category: Docampo, R]]

[[Category: Gabelli, S B]]

[[Category: McLellan, J S]]

[[Category: Montalvetti, A]]

[[Category: Oldfield, E]]

[[Category: Transferase]]