Thursday, July 17, 2025 7/17/2025

Structure and Dynamics of Cyclooxygenase Catalysis and Inhibition

Award Number: R01GM115386
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2015
PERIOD OF PERFORMANCE END DATE: 07/31/2018

Group Awards By:

View Award Description

Structure and Dynamics of Cyclooxygenase Catalysis and Inhibition - DESCRIPTION (provided by applicant): Cyclooxygenases (COX-1 and COX-2) oxygenate arachidonic acid to generate prostaglandins and are inhibited by aspirin, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and COX-2 selective diarylheterocyclic based drugs (coxibs). COX-1 and COX-2 are membrane-associated homodimers that bind to one leaflet of the lipid bilayer via a membrane-binding domain comprised of amphipathic helices. As a consequence, the enzymes have traditionally required the presence of detergents to maintain the protein in a stable and active form during functional and structural characterization. A new paradigm has emerged with respect to COX catalysis and regulation. In this model, COX functions as a conformational heterodimer with one monomer active at a given time. Common dietary FAs and nonselective NSAIDs bind to one monomer of the homodimer to modulate the oxygenation of substrates in the other monomer through an allosteric/catalytic couple. The molecular mechanism governing crosstalk between monomers is not known and static pictures derived from crystal structures of COX do not provide any insight into the conformational motions responsible for this dynamical interplay. We surmise that detergent binding and the restricted confines of the crystal lattice have masked these conformational motions. Hence, a new approach to study COX catalysis in solution and in the absence of detergent is needed. We propose to couple the use of nanodisc-reconstituted COX-2 with site- directed spin-labeling ESR spectroscopic technologies to characterize the protein conformational dynamics associated with COX catalysis and inhibition. The objectives are to identify the conformational motions responsible for: a) ligand access to the cyclooxygenase channel and b) communication between monomers. Understanding the molecular basis of how the binding of different ligands induces conformational motions responsible for crosstalk between monomers bridges the gap between the static information derived from COX crystal structure analysis and the dynamical character of COX as it relates to the modulation of COX function.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = -$5 )
2022	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	000	4	11/28/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$5
2022	2017	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	001	3	9/26/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = -$5

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	000	4	7/23/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	001	4	3/21/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$43,068
2019	2017	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	3	3/21/2019	NON-COMPETING CONTINUATION	-$43,068
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $315,013 )
2018	2018	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Biomedical Research and Research Training	001	4	9/11/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$315,013
2018	2017	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	3	9/11/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $315,013

Issue Date FY: 2017 ( Subtotal = $372,828 )
2017	2017	HAUPTMAN WOODWARD MEDICAL RESEARCH INSTITUTE, INC.	700 ELLICOTT ST	BUFFALO	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	3	7/20/2017	NON-COMPETING CONTINUATION	$372,828
														Subtotal = $372,828

Issue Date FY: 2016 ( Subtotal = $457,993 )
2016	2016	HAUPTMAN-WOODWARD MEDICAL RESEARCH INSTITUTE, INC	700 Ellicott St	Buffalo	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	2	7/14/2016	NON-COMPETING CONTINUATION	$383,150
2016	2016	HAUPTMAN-WOODWARD MEDICAL RESEARCH INSTITUTE, INC	700 Ellicott St	Buffalo	NY	14203	ERIE	USA	Biomedical Research and Research Training	001	2	7/18/2016	SUPPLEMENT FOR EXPANSION	$74,843
														Subtotal = $457,993

Issue Date FY: 2015 ( Subtotal = $383,150 )
2015	2015	HAUPTMAN-WOODWARD MEDICAL RESEARCH INSTITUTE, INC	700 Ellicott St	Buffalo	NY	14203	ERIE	USA	Biomedical Research and Research Training	000	1	7/27/2015	NEW	$383,150
														Subtotal = $383,150

Grand Total All Awards = $1,528,979

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Structure and Dynamics of Cyclooxygenase Catalysis and Inhibition

Award Number: R01GM115386

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2015

PERIOD OF PERFORMANCE END DATE: 07/31/2018

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer