8fbu | pdb_00008fbu

Crystal structure of Cryptosporidium parvum N-myristoyltransferase with bound myristoyl-CoA and Compound-2

spinqualitylabelsall models 8fbu, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fbu is a 2 chain structure with sequence from Cryptosporidium parvum Iowa II. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5CV46_CRYPI Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.[RuleBase:RU000586] Publication Abstract from PubMed Each year, approximately 50,000 children under 5 die as a result of diarrhea caused by Cryptosporidium parvum, a protozoan parasite. There are currently no effective drugs or vaccines available to cure or prevent Cryptosporidium infection, and there are limited tools for identifying and validating targets for drug or vaccine development. We previously reported a high throughput screening (HTS) of a large compound library against Plasmodium N-myristoyltransferase (NMT), a validated drug target in multiple protozoan parasite species. To identify molecules that could be effective against Cryptosporidium, we counter-screened hits from the Plasmodium NMT HTS against Cryptosporidium NMT. We identified two potential hit compounds and validated them against CpNMT to determine if NMT might be an attractive drug target also for Cryptosporidium. We tested the compounds against Cryptosporidium using both cell-based and NMT enzymatic assays. We then determined the crystal structure of CpNMT bound to Myristoyl-Coenzyme A (MyrCoA) and structures of ternary complexes with MyrCoA and the hit compounds to identify the ligand binding modes. The binding site architectures display different conformational states in the presence of the two inhibitors and provide a basis for rational design of selective inhibitors. Identification of and Structural Insights into Hit Compounds Targeting N-Myristoyltransferase for Cryptosporidium Drug Development.,Fenwick MK, Reers AR, Liu Y, Zigweid R, Sankaran B, Shin J, Hulverson MA, Hammerson B, Fernandez Alvaro E, Myler PJ, Kaushansky A, Van Voorhis WC, Fan E, Staker BL ACS Infect Dis. 2023 Oct 13;9(10):1821-1833. doi: 10.1021/acsinfecdis.3c00151. , Epub 2023 Sep 18. PMID:37722671 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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