title: Structural basis for the dimerization and substrate recognition specificity of porcine epidemic diarrhea virus 3C-like protease.
abstract: Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus, has caused significant damage to the Asian and American pork industries. Coronavirus 3C-like protease (3CL(pro)), which is involved in the processing of viral polyproteins for viral replication, is an appealing antiviral drug target. Here, we present the crystal structures of PEDV 3CL(pro) and a molecular complex between an inactive PEDV 3CL(pro) variant C144A bound to a peptide substrate. Structural characterization, mutagenesis and biochemical analysis reveal the substrate-binding pockets and the residues that comprise the active site of PEDV 3CL(pro). The dimerization of PEDV 3CL(pro) is similar to that of other Alphacoronavirus 3CL(pro)s but has several differences from that of SARS-CoV 3CL(pro) from the genus Betacoronavirus. Furthermore, the non-conserved motifs in the pockets cause different cleavage of substrate between PEDV and SARS-CoV 3CL(pro)s, which may provide new insights into the recognition of substrates by 3CL(pro)s in various coronavirus genera.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, China. Electronic address: penggq@mail.hzau.edu.cn.
authors.forename: Guiqing
authors.initials: G
authors.lastname: Peng
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D004789:Enzyme Activation; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D053485:Porcine epidemic diarrhea virus / Q000201:enzymology*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D010447:Peptide Hydrolases
keywords: Corona virus; Crystal structure; Dimerization; PEDV 3CL(pro); Substrate specificity