title: Solution structure of the 2A protease from a common cold agent, human rhinovirus C2, strain W12.
abstract: Human rhinovirus strains differ greatly in their virulence, and this has been correlated with the differing substrate specificity of the respective 2A protease (2Apro). Rhinoviruses use their 2Apro to cleave a spectrum of cellular proteins important to virus replication and anti-host activities. These enzymes share a chymotrypsin-like fold stabilized by a tetra-coordinated zinc ion. The catalytic triad consists of conserved Cys (C105), His (H34), and Asp (D18) residues. We used a semi-automated NMR protocol developed at NMRFAM to determine the solution structure of 2Apro (C105A variant) from an isolate of the clinically important rhinovirus C species (RV-C). The backbone of C2 2Apro superimposed closely (1.41-1.81 Å rmsd) with those of orthologs from RV-A2, coxsackie B4 (CB4), and enterovirus 71 (EV71) having sequence identities between 40% and 60%. Comparison of the structures suggest that the differential functional properties of C2 2Apro stem from its unique surface charge, high proportion of surface aromatics, and sequence surrounding the di-tyrosine flap.
authors.affiliation: National Magnetic Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Woonghee
authors.initials: W
authors.lastname: Lee
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Watters
authors.affiliation: Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Troupis
authors.affiliation: Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: Reinen
authors.affiliation: Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Fabian P
authors.initials: FP
authors.lastname: Suchy
authors.affiliation: Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Kylie L
authors.initials: KL
authors.lastname: Moyer
authors.affiliation: Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Ronnie O
authors.initials: RO
authors.lastname: Frederick
authors.affiliation: National Magnetic Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Aceti
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Palmenberg
authors.affiliation: National Magnetic Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Center for Eukaryotic Structural Genomics, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: John L
authors.initials: JL
authors.lastname: Markley
mesh_terms: D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012229:Rhinovirus / Q000201:enzymology*; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D014764:Viral Proteins; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus