Thursday, November 21, 2024 11/21/2024

Exploring the protein structural features which regulate myoglobin's proton transfer dependent high-valent auto-reduction

Award Number: SC2GM136557
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The goal of this study is to understand the mechanisms of the auto-reduction of high- valent iron species in two different myoglobin species, horse heart and human, in order to uncover the structural features that regulate the corresponding oxidative protein damage. Myoglobin’s propensity to oxidatively damage lipoproteins is a particular interest in the molecular mechanism of atherosclerosis. The hypothesis is that proton and electron movements that regulate the auto-reduction can inform how we study oxidative damage in proteins and atherogenic lipoproteins. To test this assumption, the mechanism will be evaluated by determining three different features. The first aim will focus on probing the kinetic and thermodynamic parameters of the auto-reduction reaction for both Mb species using transient UV-visible absorbance spectroscopy and by varying temperature and pH conditions. The second aim is to identify the proton source necessary for auto-reduction of the high-valent iron species and determine if one or more different protons are important in regulating the mechanism at physiologically low pH (inflammation sites) and neutral pH(blood based environments) utilizing kinetic solvent isotope effects, proton inventories, and site directed mutagenesis. The third aim focuses on identifying the electron donor source within the protein utilizing radical traps, tandem mass spectrometry and cyclic voltammetry.


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: 2024 ( Subtotal = -$4,357 )
2024	2022	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	3	5/14/2024	NON-COMPETING CONTINUATION	-$4,357
														Subtotal = -$4,357

Issue Date FY: 2022 ( Subtotal = $142,000 )
2022	2022	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	3	6/2/2022	NON-COMPETING CONTINUATION	$142,000
														Subtotal = $142,000

Issue Date FY: 2021 ( Subtotal = $142,000 )
2021	2021	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	2	6/22/2021	NON-COMPETING CONTINUATION	$142,000
														Subtotal = $142,000

Issue Date FY: 2020 ( Subtotal = $127,800 )
2020	2020	XAVIER UNIVERSITY OF LOUISIANA	1 DREXEL DR	NEW ORLEANS	LA	70125	ORLEANS	USA	Biomedical Research and Research Training	000	1	6/10/2020	NEW	$127,800
														Subtotal = $127,800

Grand Total All Awards = $407,443

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Exploring the protein structural features which regulate myoglobin's proton transfer dependent high-valent auto-reduction

Award Number: SC2GM136557

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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