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==Co-Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Cryptosporidium parvum and the inhibitor p131== | ==Co-Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Cryptosporidium parvum and the inhibitor p131== | ||
<StructureSection load='4rv8' size='340' side='right' caption='[[4rv8]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='4rv8' size='340' side='right'caption='[[4rv8]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4rv8]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4rv8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryptosporidium_parvum Cryptosporidium parvum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RV8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=I13:1-(2-{3-[(1E)-N-(2-AMINOETHOXY)ETHANIMIDOYL]PHENYL}PROPAN-2-YL)-3-(4-CHLORO-3-NITROPHENYL)UREA'>I13</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=I13:1-(2-{3-[(1E)-N-(2-AMINOETHOXY)ETHANIMIDOYL]PHENYL}PROPAN-2-YL)-3-(4-CHLORO-3-NITROPHENYL)UREA'>I13</scene>, <scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=4rv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rv8 OCA], [https://pdbe.org/4rv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rv8 RCSB], [https://www.ebi.ac.uk/pdbsum/4rv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rv8 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/IMDH_CRYPV IMDH_CRYPV] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (By similarity).<ref>PMID:15269207</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 18: | ||
</div> | </div> | ||
<div class="pdbe-citations 4rv8" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4rv8" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Cryptosporidium parvum]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Anderson | [[Category: Anderson WF]] | ||
[[Category: Gu M]] | |||
[[Category: Gu | [[Category: Hedstrom L]] | ||
[[Category: Hedstrom | [[Category: Joachimiak A]] | ||
[[Category: Joachimiak | [[Category: Kavitha M]] | ||
[[Category: Kavitha | [[Category: Kim Y]] | ||
[[Category: Kim | [[Category: Makowska-Grzyska M]] | ||
[[Category: Makowska-Grzyska | |||
Revision as of 11:29, 8 March 2023
Co-Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Cryptosporidium parvum and the inhibitor p131Co-Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Cryptosporidium parvum and the inhibitor p131
Structural highlights
FunctionIMDH_CRYPV Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth (By similarity).[1] Publication Abstract from PubMedInosine 5'-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment of Cryptosporidium infections. Here, the structure of C. parvum IMPDH (CpIMPDH) in complex with inosine 5'-monophosphate (IMP) and P131, an inhibitor with in vivo anticryptosporidial activity, is reported. P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO2 moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the protein. The design of compounds to replace these water molecules is a new strategy for the further optimization of C. parvum inhibitors for both antiparasitic and antibacterial applications. Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity.,Kim Y, Makowska-Grzyska M, Gorla SK, Gollapalli DR, Cuny GD, Joachimiak A, Hedstrom L Acta Crystallogr F Struct Biol Commun. 2015 May;71(Pt 5):531-8. doi:, 10.1107/S2053230X15000187. Epub 2015 Apr 21. PMID:25945705[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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