Long-range cooperative interactions modulate dimerization in SARS 3CLpro.

Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Abstract Text:

Jennifer Barrila,Usman Bacha,Ernesto Freire,

Severe acute respiratory syndrome (SARS) is an infectious disease caused by the human coronavirus, SARS-CoV. The main viral protease, SARS 3CLpro, is a validated target for the development of antiviral therapies. Since the enzyme is a homodimer and the individual monomers are inactive, two approaches are being used to develop inhibitors: enzyme activity inhibitors that target the active site and dimerization inhibitors. Dimerization inhibitors are usually targeted to the dimerization interface and need to compete with the attractive forces between subunits to be effective. In this paper, we show that the dimerization of SARS 3CLpro is also under allosteric control and that additional and energetically more favorable target sites away from the dimerization interface may also lead to subunit dissociation. We previously identified a cluster of conserved serine residues (Ser139, Ser144, and Ser147) located adjacent to the active site of 3CLpro that could effectively be targeted to inactivate the protease [Bacha, U et al. (2004) Biochemistry 43, 4906-4912]. Mutation of any of these serine residues to alanine had a debilitating effect on the catalytic activity of 3CLpro. In particular, the mutation of Ser147, which does not make any contact with the opposing subunit and is located approximately 9 A away from the dimer interface, totally inhibited dimerization and resulted in a complete loss of enzymatic activity. The finding that residues away from the dimer interface are able to control dimerization defines alternative targets for the design of dimerization inhibitors.

Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Publishing Authors By Initials

J Barrila,U Bacha,E Freire,

For similar proteins: viral proteins research abstracts see: proteins: viral proteins research

PUBMED ID PMID:

MEDLINE DATE:

Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemistry

VOLUME: 45

Page Numbers: 14908-16

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 19

MONTH: Dec

YEAR: 2006

Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Keywords Mesh Terms:

KEYWORDS: Viral Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Long-range cooperative interactions modulate dimerization in SARS 3CLpro. Information

Substance Name: Cysteine Endopeptidases

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Long-range cooperative interactions modulate dimerization in SARS 3CLpro.

AFFILIATION: Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM57144

ACRONYM: GM

MEDLINETA: Biochemistry

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Long-range cooperative interactions modulate dimerization in SARS 3CLpro Related Publications

• Acetone powder from dormant seeds of Ricinus communis L : Lipase activity and presence of toxic and allergenic compounds.
• Cajal's contributions to the study of Alzheimer's disease.
• Cleavage and degradation of Claspin during apoptosis by caspases and the proteasome.
• Compensating enthalpic and entropic changes hinder binding affinity optimization.
• Copper acetylacetonate anchored onto amine-functionalised clays.
• Correlation between Enterococcus faecalis Biofilms Development Stage and Quantitative Surface Roughness Using Atomic Force Microscopy.
• Diagnosis of canine brucellosis by ELISA using an antigen obtained from wild Brucella canis.
• Extracellular methylglyoxal toxicity in Saccharomyces cerevisiae: role of glucose and phosphate ions.
• Inhibition of HIV-2 Protease by HIV-1 Protease Inhibitors in Clinical Use.
• Isothermal titration calorimetry to determine association constants for high-affinity ligands.
• Isothermal titration calorimetry.
• Long-range cooperative interactions modulate dimerization in SARS 3CLpro.
• Moisture adsorption and desorption behavior of sludge powder.
• Oral health status of 207 head and neck cancer patients before, during and after radiotherapy.
• Pressure-inactivated yellow fever 17DD virus: Implications for vaccine development.
• Prevalence and intensity of pentastomid infection in two species of snakes from northeastern Brazil.
• Prevalence of attention deficit hyperactivity disorder in schoolchildren in the city of Salvador, Bahia, Brazil.
• Protein glycation and methylglyoxal metabolism in yeast: finding peptide needles in protein haystacks.
• Rhabdomyolysis in a patient with West Nile encephalitis and flaccid paralysis.
• Straight talk with... Maria Freire. Interviewed by Alisa Opar.
• The Brachyura and Anomura fauna (Decapoda; Crustacea) in the Arvoredo Marine Biological Reserve on the southern Brazilian coast.
• The age of the tumor-bearing hosts as a factor conditioning the transmissibility of the Rous sarcoma by filtrates and cells.
• The native-state ensemble of proteins provides clues for folding, misfolding and function.
• The role of short-ranged energetic correlations in the mobility field dependence of disordered organic materials.
• Theoretical and experimental studies of the photoluminescent properties of the coordination polymer [Eu(DPA)(HDPA)(H2O)2].4H2O.
• Unique thermodynamic response of tipranavir to human immunodeficiency virus type 1 protease drug resistance mutations.
• Vertical echosounder versus side-scan sonar mapping of Posidonia Oceanica fields.
• [Epidemiology of enterovirus associated with neurologic diseases]
• [Health policy in the European Union: impact on the Spanish health system]
• [Relation between the resistance index obtained by the transfontanellar Doppler ultrasonography and the neurological development until the first year of life in term infants with mild or moderate hypoxic-ischaemic encephalopathy.]