Structure of adenovirus bound to cellular receptor car
Abstract
Disclosed is a mutant adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have significantly weakened binding affinity for CARD1 relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type. In the method, residues of the adenovirus fiber protein knob domain which are predicted to alter D1 binding when mutated, are identified from the crystal structure coordinates of the AD12knob:CAR-D1 complex. A mutation which alters one or more of the identified residues is introduced into the genome of the adenovirus to generate a mutant adenovirus. Whether or not the mutant produced exhibits altered adenovirus-CAR binding properties is then determined.
- Inventors:
- Issue Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1174848
- Patent Number(s):
- 6737234
- Application Number:
- 09/389,603
- Assignee:
- Brookhaven Science Associates, LCC (Upton, NY)
- Patent Classifications (CPCs):
-
A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES
- DOE Contract Number:
- AC02-98CH10886
- Resource Type:
- Patent
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Freimuth, Paul I. Structure of adenovirus bound to cellular receptor car. United States: N. p., 2004.
Web.
Freimuth, Paul I. Structure of adenovirus bound to cellular receptor car. United States.
Freimuth, Paul I. Tue .
"Structure of adenovirus bound to cellular receptor car". United States. https://www.osti.gov/servlets/purl/1174848.
@article{osti_1174848,
title = {Structure of adenovirus bound to cellular receptor car},
author = {Freimuth, Paul I.},
abstractNote = {Disclosed is a mutant adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have significantly weakened binding affinity for CARD1 relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type. In the method, residues of the adenovirus fiber protein knob domain which are predicted to alter D1 binding when mutated, are identified from the crystal structure coordinates of the AD12knob:CAR-D1 complex. A mutation which alters one or more of the identified residues is introduced into the genome of the adenovirus to generate a mutant adenovirus. Whether or not the mutant produced exhibits altered adenovirus-CAR binding properties is then determined.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue May 18 00:00:00 EDT 2004},
month = {Tue May 18 00:00:00 EDT 2004}
}
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