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The Crystal Structure of Cryptosporidium parvum Inosine-5'-Monophosphate DehydrogenaseThe Crystal Structure of Cryptosporidium parvum Inosine-5'-Monophosphate Dehydrogenase
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] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and a major cause of diarrhea and malnutrition. No vaccines or effective drug treatment exist to combat Cryptosporidium infection. This parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) to obtain guanine nucleotides, and inhibition of this enzyme blocks parasite proliferation. Here, we report the first crystal structures of CpIMPDH. These structures reveal the structural basis of inhibitor selectivity and suggest a strategy for further optimization. Using this information, we have synthesized low-nanomolar inhibitors that display 10(3) selectivity for the parasite enzyme over human IMPDH2. The Structural Basis of Cryptosporidium -Specific IMP Dehydrogenase Inhibitor Selectivity.,Macpherson IS, Kirubakaran S, Gorla SK, Riera TV, D'Aquino JA, Zhang M, Cuny GD, Hedstrom L J Am Chem Soc. 2010 Jan 6. PMID:20052976[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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