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Redox cofactor diversification in enzyme superfamilies

Award Number: R35GM136294
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: 06/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Redox cofactor diversification in enzyme superfamilies - PROJECT ABSTRACT The availability of microbial genomic information continues to provide vast opportunities to reveal unknown chemistry. But as we continue to gather more and more genomic sequence information, the larger challenge of translating that sequence based information into insight about novel enzymatic processes and/or biosynthetic pathways remains. The challenge is even greater when considering metalloproteins and enzymes: such proteins are thought to be > 30% of all protein content, yet accurate bioinformatic prediction of metalloprotein properties (even metal binding) is severely limited, yet metalloenzymes are responsible to achieve Nature's hardest chemical transformations. Discovering and understanding the basis of metalloprotein- based catalysis underpins the deep efforts that are required to land on new strategies for the development of therapeutic agents, or to understand many disease processes. The focus of this R35 renewal proposal is to continue the development of work-flows that combine bionformatic discovery-oriented science, with the evaluation of how the same protein fold and metallocofactors are used by nature to achieve diverse biochemical transformations. This application will largely focus on members of the diheme enzyme family referred to as bacterial cytochrome c peroxidases (bCCPs) as well as AdoMet Radical Enzymes (AREs). Here a combination of bioinformatic, biochemical, structural, spectroscopic, electrochemical and computational tools will be integrated to examine mechanistic questions of how these enzymes can manipulate the same redox- active metallocofactors in distinct modes, and to reveal the novel chemistry of new family members. The proposed studies marry our interests in enzymoloy, bioinformatics and biophysical chemistry, to probe the diversity of nature's redox enzymes, revealing not only what is possible in the chemistry of these remarkable catalysts, but how nature masters the desired reactivity with the correct metallocofactor.


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: 2026 ( Subtotal = $548,045 )
2026	2026	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	6	7/3/2026	COMPETING CONTINUATION	$548,045
														Subtotal = $548,045

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	5	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $495,000 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	5	5/2/2024	NON-COMPETING CONTINUATION	$495,000
														Subtotal = $495,000

Issue Date FY: 2023 ( Subtotal = $627,241 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	001	4	6/7/2023	SUPPLEMENT FOR EXPANSION	$132,241
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	4	5/4/2023	NON-COMPETING CONTINUATION	$495,000
														Subtotal = $627,241

Issue Date FY: 2022 ( Subtotal = $495,000 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	3	5/17/2022	NON-COMPETING CONTINUATION	$495,000
														Subtotal = $495,000

Issue Date FY: 2021 ( Subtotal = $495,000 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	2	5/26/2021	NON-COMPETING CONTINUATION	$495,000
														Subtotal = $495,000

Issue Date FY: 2020 ( Subtotal = $264,482 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	1	4/22/2020	NEW	$264,482
														Subtotal = $264,482

Grand Total All Awards = $2,924,768

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Redox cofactor diversification in enzyme superfamilies

Award Number: R35GM136294

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: 06/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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