Friday, November 22, 2024 11/22/2024

Structure and Mechanism of the Human FE-S Cluster Assembly Complex

Award Number: R01GM096100
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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View Award Abstract

Metal ions are essential to life as they augment amino acid protein chemistry and thereby catalyze many difficult biological reactions. As “free” metal ions are toxic and indiscriminately reactive, critical protein systems have evolved to sequester, chaperone, and regulate metal ion concentrations. Defects in these systems lead to metal ion metabolic disease and result in cellular, tissue, and systemic pathology. The iron-sulfur cluster assembly pathway contains a conserved set of metallochaperone proteins that recognize and insert Fe-S clusters into apo metalloproteins. We determined the first crystal structure for the NFS1-ISD11-ACP cysteine desulfurase, which is a central enzyme in this pathway that is also implicated in providing sulfur for molybdenum cofactor biosynthesis and tRNA modifications. Interestingly, three distinct interchangeable α2β22 architectures are now known for the cysteine desulfurase complex that have superimposable protomers but distinct protein-protein interactions. In this proposal, we aim to investigate the functional relationship between these architectures, elucidate mechanistic details for sulfur transfer to different acceptor proteins and for Fe-S cluster assembly, and provide new insight into the regulatory control mechanisms for human Fe-S cluster biosynthesis. This fundamental research will establish a framework for emerging genetic results and discoveries and provide a basis for understanding defects in iron-sulfur cluster metabolism relevant to human health and disease.


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 = $290,301 )
2024	2024	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	12	3/26/2024	NON-COMPETING CONTINUATION	$261,271
2024	2024	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	12	7/25/2024	NON-COMPETING CONTINUATION	$29,030
														Subtotal = $290,301

Issue Date FY: 2023 ( Subtotal = $404,311 )
2023	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	11	5/19/2023	SUPPLEMENT FOR EXPANSION	$99,183
2023	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	002	11	5/23/2023	SUPPLEMENT FOR EXPANSION	$13,862
2023	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	11	3/2/2023	NON-COMPETING CONTINUATION	$291,266
														Subtotal = $404,311

Issue Date FY: 2022 ( Subtotal = $292,186 )
2022	2022	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	10	5/16/2022	NON-COMPETING CONTINUATION	$29,219
2022	2022	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	10	2/28/2022	NON-COMPETING CONTINUATION	$262,967
														Subtotal = $292,186

Issue Date FY: 2021 ( Subtotal = $293,061 )
2021	2021	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	9	6/23/2021	COMPETING CONTINUATION	$293,061
2021	2021	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	002	9	7/30/2021	COMPETING CONTINUATION	$363
2021	2020	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	8	7/30/2021	NON-COMPETING CONTINUATION	-$363
														Subtotal = $293,061

Issue Date FY: 2020 ( Subtotal = $285,099 )
2020	2020	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	8	1/16/2020	NON-COMPETING CONTINUATION	$256,589
2020	2020	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	8	3/6/2020	NON-COMPETING CONTINUATION	$28,510
														Subtotal = $285,099

Issue Date FY: 2019 ( Subtotal = $285,666 )
2019	2019	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	7	1/24/2019	NON-COMPETING CONTINUATION	$285,666
														Subtotal = $285,666

Issue Date FY: 2018 ( Subtotal = $286,205 )
2018	2018	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	6	5/15/2018	NON-COMPETING CONTINUATION	$28,621
2018	2018	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	6	1/19/2018	NON-COMPETING CONTINUATION	$257,584
														Subtotal = $286,205

Issue Date FY: 2017 ( Subtotal = $286,719 )
2017	2017	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	003	5	9/9/2017	COMPETING CONTINUATION	$2,659
2017	2017	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	001	5	4/3/2017	COMPETING CONTINUATION	$286,719
2017	2014	TEXAS A & M RESEARCH FOUNDATION	400 HARVEY MITCHELL PKWY STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	002	4	9/9/2017	NON-COMPETING CONTINUATION	-$2,659
2017	2014	TEXAS A & M RESEARCH FOUNDATION	400 HARVEY MITCHELL PKWY STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	4	3/29/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $286,719

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	4	5/4/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $269,394 )
2014	2014	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	4	5/12/2014	NON-COMPETING CONTINUATION	$269,394
														Subtotal = $269,394

Issue Date FY: 2013 ( Subtotal = $259,965 )
2013	2013	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	3	5/30/2013	NON-COMPETING CONTINUATION	$259,965
														Subtotal = $259,965

Issue Date FY: 2012 ( Subtotal = $269,394 )
2012	2012	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	2	5/16/2012	NON-COMPETING CONTINUATION	$269,394
														Subtotal = $269,394

Issue Date FY: 2011 ( Subtotal = $248,457 )
2011	2011	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Biomedical Research and Research Training	000	1	8/16/2011	NEW	$248,457
														Subtotal = $248,457

Grand Total All Awards = $3,470,758

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Structure and Mechanism of the Human FE-S Cluster Assembly Complex

Award Number: R01GM096100

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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