2q58

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[[Image:2q58.gif|left|200px]]
 
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==Cryptosporidium parvum putative polyprenyl pyrophosphate synthase (cgd4_2550) in complex with zoledronate==
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The line below this paragraph, containing "STRUCTURE_2q58", creates the "Structure Box" on the page.
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<StructureSection load='2q58' size='340' side='right'caption='[[2q58]], [[Resolution|resolution]] 2.37&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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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]] 2.37&#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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZOL:ZOLEDRONIC+ACID'>ZOL</scene></td></tr>
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{{STRUCTURE_2q58| PDB=2q58 | SCENE= }}
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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=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>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q5CR09_CRYPI Q5CR09_CRYPI]
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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/q5/2q58_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=2q58 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''Cryptosporidium parvum putative polyprenyl pyrophosphate synthase (cgd4_2550) in complex with zoledronate'''
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==Overview==
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</div>
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Parasites from the protozoan phylum Apicomplexa are responsible for diseases, such as malaria, toxoplasmosis and cryptosporidiosis, all of which have significantly higher rates of mortality and morbidity in economically underdeveloped regions of the world. Advances in vaccine development and drug discovery are urgently needed to control these diseases and can be facilitated by production of purified recombinant proteins from Apicomplexan genomes and determination of their 3D structures. To date, both heterologous expression and crystallization of Apicomplexan proteins have seen only limited success. In an effort to explore the effectiveness of producing and crystallizing proteins on a genome-scale using a standardized methodology, over 400 distinct Plasmodium falciparum target genes were chosen representing different cellular classes, along with select orthologues from four other Plasmodium species as well as Cryptosporidium parvum and Toxoplasma gondii. From a total of 1008 genes from the seven genomes, 304 (30.2%) produced purified soluble proteins and 97 (9.6%) crystallized, culminating in 36 crystal structures. These results demonstrate that, contrary to previous findings, a standardized platform using Escherichia coli can be effective for genome-scale production and crystallography of Apicomplexan proteins. Predictably, orthologous proteins from different Apicomplexan genomes behaved differently in expression, purification and crystallization, although the overall success rates of Plasmodium orthologues do not differ significantly. Their differences were effectively exploited to elevate the overall productivity to levels comparable to the most successful ongoing structural genomics projects: 229 of the 468 target genes produced purified soluble protein from one or more organisms, with 80 and 32 of the purified targets, respectively, leading to crystals and ultimately structures from one or more orthologues.
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<div class="pdbe-citations 2q58" style="background-color:#fffaf0;"></div>
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== References ==
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==About this Structure==
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<references/>
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2Q58 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Cryptosporidium_parvum_iowa_ii Cryptosporidium parvum iowa ii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q58 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Cryptosporidium parvum Iowa II]]
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Genome-scale protein expression and structural biology of Plasmodium falciparum and related Apicomplexan organisms., Vedadi M, Lew J, Artz J, Amani M, Zhao Y, Dong A, Wasney GA, Gao M, Hills T, Brokx S, Qiu W, Sharma S, Diassiti A, Alam Z, Melone M, Mulichak A, Wernimont A, Bray J, Loppnau P, Plotnikova O, Newberry K, Sundararajan E, Houston S, Walker J, Tempel W, Bochkarev A, Kozieradzki I, Edwards A, Arrowsmith C, Roos D, Kain K, Hui R, Mol Biochem Parasitol. 2007 Jan;151(1):100-10. Epub 2006 Nov 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17125854 17125854]
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[[Category: Large Structures]]
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[[Category: Cryptosporidium parvum iowa ii]]
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[[Category: Arrowsmith C]]
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[[Category: Single protein]]
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[[Category: Artz J]]
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[[Category: Arrowsmith, C.]]
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[[Category: Bochkarev A]]
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[[Category: Artz, J.]]
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[[Category: Chruszcz M]]
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[[Category: Bochkarev, A.]]
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[[Category: Dong A]]
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[[Category: Chruszcz, M.]]
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[[Category: Dunford J]]
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[[Category: Dong, A.]]
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[[Category: Edwards A]]
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[[Category: Dunford, J.]]
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[[Category: Hui R]]
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[[Category: Edwards, A.]]
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[[Category: Kavanaugh KL]]
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[[Category: Hui, R.]]
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[[Category: Kozieradski I]]
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[[Category: Kavanaugh, K L.]]
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[[Category: Lew J]]
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[[Category: Kozieradski, I.]]
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[[Category: Minor W]]
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[[Category: Lew, J.]]
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[[Category: Opperman U]]
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[[Category: Minor, W.]]
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[[Category: Sundstrom M]]
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[[Category: Opperman, U.]]
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[[Category: Weigelt J]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Zhao Y]]
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[[Category: Sundstrom, M.]]
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[[Category: Zheng H]]
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[[Category: Weigelt, J.]]
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[[Category: Zhao, Y.]]
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[[Category: Zheng, H.]]
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[[Category: Farnesyl diphosphate synthase]]
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[[Category: Sgc]]
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[[Category: Structural genomic]]
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[[Category: Structural genomics consortium]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:22:56 2008''
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Current revision

Cryptosporidium parvum putative polyprenyl pyrophosphate synthase (cgd4_2550) in complex with zoledronate

PDB ID 2q58

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