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Solution structure of the 2A protease from a common cold agent, human rhinovirus C2, strain W12.

Lee W, Watters KE, Troupis AT, Reinen NM, Suchy FP, Moyer KL, Frederick RO, Tonelli M, Aceti DJ, Palmenberg AC, Markley JL - PLoS ONE (2014)

Bottom Line: The catalytic triad consists of conserved Cys (C105), His (H34), and Asp (D18) residues.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.

View Article: PubMed Central - PubMed

Affiliation: National Magnetic Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

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.

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Relaxation times and heteronuclear NOEs.(A) Longitudinal (T1) relaxation times, (B) transverse (T2) relaxation times, and (C) 1H-15N heteronuclear NOE data for the nitrogen backbone atoms of C2 2Apro plotted as a function of the amino acid sequence. The standard errors for all measurements were within the size of the data points shown.
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pone-0097198-g006: Relaxation times and heteronuclear NOEs.(A) Longitudinal (T1) relaxation times, (B) transverse (T2) relaxation times, and (C) 1H-15N heteronuclear NOE data for the nitrogen backbone atoms of C2 2Apro plotted as a function of the amino acid sequence. The standard errors for all measurements were within the size of the data points shown.

Mentions: Longitudinal (T1) and transverse (T2) 15N relaxation data as well as 1H-15N heteronuclear NOE data (Figure 6) were collected to explore the dynamic behavior of C2 2Apro. We used Eq. 1 to estimate the overall correlation time (τc) from the T1/T2 ratios of residues involved in elements of secondary structure.


Solution structure of the 2A protease from a common cold agent, human rhinovirus C2, strain W12.

Lee W, Watters KE, Troupis AT, Reinen NM, Suchy FP, Moyer KL, Frederick RO, Tonelli M, Aceti DJ, Palmenberg AC, Markley JL - PLoS ONE (2014)

Relaxation times and heteronuclear NOEs.(A) Longitudinal (T1) relaxation times, (B) transverse (T2) relaxation times, and (C) 1H-15N heteronuclear NOE data for the nitrogen backbone atoms of C2 2Apro plotted as a function of the amino acid sequence. The standard errors for all measurements were within the size of the data points shown.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061012&req=5

pone-0097198-g006: Relaxation times and heteronuclear NOEs.(A) Longitudinal (T1) relaxation times, (B) transverse (T2) relaxation times, and (C) 1H-15N heteronuclear NOE data for the nitrogen backbone atoms of C2 2Apro plotted as a function of the amino acid sequence. The standard errors for all measurements were within the size of the data points shown.
Mentions: Longitudinal (T1) and transverse (T2) 15N relaxation data as well as 1H-15N heteronuclear NOE data (Figure 6) were collected to explore the dynamic behavior of C2 2Apro. We used Eq. 1 to estimate the overall correlation time (τc) from the T1/T2 ratios of residues involved in elements of secondary structure.

Bottom Line: The catalytic triad consists of conserved Cys (C105), His (H34), and Asp (D18) residues.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.

View Article: PubMed Central - PubMed

Affiliation: National Magnetic Resonance Facility at Madison, Biochemistry Department, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

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.

Show MeSH
Related in: MedlinePlus