View source for 2q58


==Cryptosporidium parvum putative polyprenyl pyrophosphate synthase (cgd4_2550) in complex with zoledronate==
<StructureSection load='2q58' size='340' side='right'caption='[[2q58]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2q58]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_parvum_Iowa_II Cryptosporidium parvum Iowa II]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2her 2her]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q58 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q58 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.37&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZOL:ZOLEDRONIC+ACID'>ZOL</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2q58 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q58 OCA], [https://pdbe.org/2q58 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q58 RCSB], [https://www.ebi.ac.uk/pdbsum/2q58 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q58 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5CR09_CRYPI Q5CR09_CRYPI] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q5/2q58_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2q58 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cryptosporidiosis is a neglected disease without a wholly effective drug. We present a study demonstrating nitrogen-containing bisphosphonates (N-BPs) to be capable of inhibiting Cryptosporidium parvum at low micromolar concentrations in infected MDCK cells. Predictably, the mechanism of action is based on inhibition of biosynthesis of isoprenoids but the target enzyme is unexpectedly a distinctive C. parvum enzyme dubbed nonspecific polyprenyl pyrophosphate synthase (CpNPPPS). This enzyme produces various isoprenoid products larger than FPP and is inhibited by N-BPs at subnanomolar concentrations. It is part of an isoprenoid pathway in Cryptosporidium distinctly different from other organisms. The proposed mechanism of action is corroborated by crystal structures of the enzyme with risedronate and zoledronate bound showing how this enzyme's unique chain length determinant region enables it to accommodate larger substrates and products. These results, combined with existing data on their clinical use, demonstrate that N-BPs are very promising anticryptosporidial drug candidates.

Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis.,Artz JD, Dunford JE, Arrowood MJ, Dong A, Chruszcz M, Kavanagh KL, Minor W, Russell RG, Ebetino FH, Oppermann U, Hui R Chem Biol. 2008 Dec 22;15(12):1296-306. PMID:19101474<ref>PMID:19101474</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2q58" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cryptosporidium parvum Iowa II]]
[[Category: Large Structures]]
[[Category: Arrowsmith C]]
[[Category: Artz J]]
[[Category: Bochkarev A]]
[[Category: Chruszcz M]]
[[Category: Dong A]]
[[Category: Dunford J]]
[[Category: Edwards A]]
[[Category: Hui R]]
[[Category: Kavanaugh KL]]
[[Category: Kozieradski I]]
[[Category: Lew J]]
[[Category: Minor W]]
[[Category: Opperman U]]
[[Category: Sundstrom M]]
[[Category: Weigelt J]]
[[Category: Zhao Y]]
[[Category: Zheng H]]