5dp3

Crystal Structure of EV71 3C Proteinase in complex with compound 2Crystal Structure of EV71 3C Proteinase in complex with compound 2

Structural highlights 5dp3 is a 1 chain structure with sequence from Ev-71. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 5dp4, 5dp5, 5dp6, 5dp7, 5dp8, 5dp9, 5dpa Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [A9XG43_9ENTO] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[SAAS:SAAS000199_004_016611] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[SAAS:SAAS000199_004_042266] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[SAAS:SAAS000199_004_010047] Publication Abstract from PubMed BACKGROUND: Enterovirus 71 (EV71) is a causative agent of hand, foot and mouth disease (HFMD), which can spread its infection to central nervous and other systems with severe consequence. A key factor in the replication of EV71 is its 3C proteinase (3C(pro)), a significant drug target. Peptidomimetics were employed as inhibitors of this enzyme for developing antivirals. However, the peptide bonds in these peptidomimetics are a source of low bioavailability due to their susceptibility to protease digestion. To produce non-peptidomimetic inhibitors by replacing these peptide bonds, it would be important to gain better understanding on the contribution of each component to the interaction and potency. METHODS: A series of compounds of different lengths targeting 3C(pro) and having an alpha,beta-unsaturated ester as the warhead were synthesized and their interactions with the enzyme were evaluated by complex structure analyses and potency assays for a better understanding on the relationship between potency and evolution of interaction. RESULTS: The P2 moiety of the compound would need to be oriented to interact in the S2 site in the substrate binding cleft and the P3-P4 moieties were required to generate sufficient potency. A hydrophobic terminal group will benefit the cellular uptake and improve the activity in vivo. CONCLUSIONS AND GENERAL SIGNIFICANCE: The data presented here provide a basis for designing a new generation of non-peptidomimetics to target EV71 3C(pro). Fragment-wise design of inhibitors to 3C proteinase from enterovirus 71.,Wu C, Zhang L, Li P, Cai Q, Peng X, Yin K, Chen X, Ren H, Zhong S, Weng Y, Guan Y, Chen S, Wu J, Li J, Lin T Biochim Biophys Acta. 2016 Jun;1860(6):1299-307. doi:, 10.1016/j.bbagen.2016.03.017. Epub 2016 Mar 15. PMID:26987809 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 5dp3, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image