{"metadata":{"accession":"PS51874","entry_id":null,"type":"domain","go_terms":null,"source_database":"profile","member_databases":null,"integrated":"IPR044067","hierarchy":null,"name":{"name":"Picornavirales 3C/3C-like protease domain profile","short":"PCV_3C_PRO"},"description":[{"text":"<p>Viruses in the order Picornavirales infect different vertebrate, invertebrate,\nand plant hosts and are responsible for a variety of human, animal, and plant\ndiseases. Viruses in this order have a single-stranded, positive sense RNA\n(+ssRNA) genome that generally translates a large precusrsor polyprotein.\nAfter translation, the viral precursor polyprotein is proteolytically cleaved\nto generate mature functional viral proteins. This maturation process is\nusually mediated by (more than one) proteases, and a 3C (for the family\nPicornaviridae) or 3C-like (3CL) protease (for other families) plays a central\nrole in the cleavage of the viral precursor polyprotein. In addition to its\nkey role in processing the polyprotein, 3C/3C-like protease is able to cleave\na number of host proteins to remodel the cellular environment for virus\nreproduction [[cite:PUB00032759]][[cite:PUB00094816]][[cite:PUB00050441]][[cite:PUB00056357]][[cite:PUB00056400]][[cite:PUB00094817]]. The Picornavirales 3C/3C-like protease domain\nforms the peptidase family C3 (picornain family) of clan PA [E1].\n\nThe 3C/3CL protease domain adopts a chymotrypsin-like fold with a cysteine\nnucleophile in place of a commonly found serine. Accordingly, 3C and 3C-like\nproteases partially tolerate a replacement of the catalytic cysteine by a\nserine, and vice-versa, suggesting that the cysteine and serine perform an\nanalogous catalytic function. The catalytic triad is made of a histidine, an\naspartate/glutamate and the conserved cysteine in this sequential order. The\n3C/3CL protease domain folds into two antiparallel beta barrels that are\nlinked by a loop with a short alpha-helix in its middle, and flanked by two\nother alpha-helices at the N- and C-termini. The two barrels\nare topologically equivalent and are formed by six antiparallel beta strands\nwith the first four organized into a Greek key motif. The active-site residues\nare located in the cleft between the two barrels with the nucleophilic Cys\nfrom the C-terminal barrel and the general acid base His-Glu/Asp from the N-\nterminal barrel [[cite:PUB00032759]][[cite:PUB00094816]][[cite:PUB00056357]].\n\nThe profile we developed covers the entire 3C/3C-like protease domain.</p>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00056400":{"PMID":21795339,"ISBN":null,"volume":"85","issue":"19","year":2011,"title":"Enterovirus 71 and Coxsackievirus A16 3C Proteases: Binding to Rupintrivir and Their Substrates and Anti-Hand, Foot, and Mouth Disease Virus Drug Design.","URL":null,"raw_pages":"10319-31","medline_journal":"J Virol","ISO_journal":"J. Virol.","authors":["Lu G","Qi J","Chen Z","Xu X","Gao F","Lin D","Qian W","Liu H","Jiang H","Yan J","Gao GF."],"DOI_URL":null},"PUB00032759":{"PMID":15654079,"ISBN":null,"volume":"280","issue":"12","year":2005,"title":"Crystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity.","URL":null,"raw_pages":"11520-7","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Birtley JR","Knox SR","Jaulent AM","Brick P","Leatherbarrow RJ","Curry S."],"DOI_URL":"http://dx.doi.org/10.1074/jbc.M413254200"},"PUB00050441":{"PMID":19144641,"ISBN":null,"volume":"284","issue":"12","year":2009,"title":"Structural basis of inhibition specificities of 3C and 3C-like proteases by zinc-coordinating and peptidomimetic compounds.","URL":null,"raw_pages":"7646-55","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Lee CC","Kuo CJ","Ko TP","Hsu MF","Tsui YC","Chang SC","Yang S","Chen SJ","Chen HC","Hsu MC","Shih SR","Liang PH","Wang AH."],"DOI_URL":"http://dx.doi.org/10.1074/jbc.M807947200"},"PUB00094817":{"PMID":22534091,"ISBN":null,"volume":"428","issue":"2","year":2012,"title":"Identification and characterization of Iflavirus 3C-like protease processing activities.","URL":null,"raw_pages":"136-45","medline_journal":"Virology","ISO_journal":"Virology","authors":["Ye S","Xia H","Dong C","Cheng Z","Xia X","Zhang J","Zhou X","Hu Y."],"DOI_URL":null},"PUB00094816":{"PMID":18293057,"ISBN":null,"volume":"153","issue":"4","year":2008,"title":"Picornavirales, a proposed order of positive-sense single-stranded RNA viruses with a pseudo-T = 3 virion architecture.","URL":null,"raw_pages":"715-27","medline_journal":"Arch Virol","ISO_journal":"Arch. Virol.","authors":["Le Gall O","Christian P","Fauquet CM","King AM","Knowles NJ","Nakashima N","Stanway G","Gorbalenya AE."],"DOI_URL":null},"PUB00056357":{"PMID":21835784,"ISBN":null,"volume":null,"issue":null,"year":2011,"title":"Structural basis for antiviral inhibition of the main protease 3C from human enterovirus 93.","URL":null,"raw_pages":null,"medline_journal":"J Virol","ISO_journal":"J. Virol.","authors":["Costenaro L","Kaczmarska Z","Arnan C","Janowski R","Coutard B","Sola M","Gorbalenya AE","Norder H","Canard B","Coll M."],"DOI_URL":null}},"set_info":null,"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":0,"interactions":0,"matches":14202,"pathways":0,"proteins":14202,"proteomes":254,"sets":0,"structural_models":{"alphafold":35,"bfvd":106},"structures":219,"taxa":2071},"entry_annotations":{},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"7quw","name":"CVB3-3Cpro in complex with inhibitor MG-78"}}}