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Substrate Channeling and Communication in Proline Metabolic Enzymes

Award Number: R01GM065546
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: 05/05/2002
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Substrate Channeling and Communication in Proline Metabolic Enzymes - PROJECT SUMMARY Metabolic enzymes in cells rarely function in isolation. Often their activities are coordinated by physical or covalent association with each other and cellular structures. A consequence of these associations is that metabolic intermediates do not equilibrate with the cellular milieu and are instead channeled between enzyme active sites. Despite the widespread recognition that protein-protein interactions are ubiquitous, the molecular mechanisms of substrate channeling remain obscure, and the impact of channeling at the cellular and organismal levels is largely unknown. We seek to narrow these knowledge gaps by exploring substrate channeling within and between the enzymes of proline catabolism. The proposed experiments will explore long-distance, allosteric communication between the active sites of the bifunctional enzyme PutA using kinetic crystallography, assess the contributions of substrate channeling to bacterial fitness and pathogenesis, and determine the first structure of a novel bifunctional enzyme that moonlights as a transcriptional repressor using cryo-EM.


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 = $442,340 )
2026	2026	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	16	4/17/2026	NON-COMPETING CONTINUATION	$442,340
														Subtotal = $442,340

Issue Date FY: 2025 ( Subtotal = $442,340 )
2025	2025	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	15	4/24/2025	NON-COMPETING CONTINUATION	$442,340
														Subtotal = $442,340

Issue Date FY: 2024 ( Subtotal = $493,739 )
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	14	5/8/2024	NON-COMPETING CONTINUATION	$442,340
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	001	14	8/21/2024	SUPPLEMENT FOR EXPANSION	$51,399
														Subtotal = $493,739

Issue Date FY: 2023 ( Subtotal = $456,465 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	13	5/23/2023	COMPETING CONTINUATION	$456,465
														Subtotal = $456,465

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2018	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	12	8/25/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	12	4/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	12	4/9/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $303,417 )
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	12	4/23/2018	NON-COMPETING CONTINUATION	$303,417
														Subtotal = $303,417

Issue Date FY: 2017 ( Subtotal = $418,862 )
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	001	11	6/2/2017	NON-COMPETING CONTINUATION	$41,887
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	11	4/17/2017	NON-COMPETING CONTINUATION	$376,975
														Subtotal = $418,862

Issue Date FY: 2016 ( Subtotal = $461,039 )
2016	2016	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Biomedical Research and Research Training	000	10	4/19/2016	NON-COMPETING CONTINUATION	$280,541
2016	2016	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Biomedical Research and Research Training	001	10	7/18/2016	SUPPLEMENT FOR EXPANSION	$69,861
2016	2016	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Biomedical Research and Research Training	002	10	9/14/2016	SUPPLEMENT FOR EXPANSION	$110,637
														Subtotal = $461,039

Issue Date FY: 2015 ( Subtotal = $294,108 )
2015	2015	CURATORS OF THE UNIVERSITY OF MISSOURI	5100 Rockhill Road	Kansas City	MO	64110	JACKSON	USA	Biomedical Research and Research Training	000	9	7/24/2015	COMPETING CONTINUATION	$294,108
														Subtotal = $294,108

Issue Date FY: 2011 ( Subtotal = $273,646 )
2011	2011	CURATORS OF THE UNIVERSITY OF MISSOURI	310 Jesse Hall	Columbia	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	8	4/4/2011	NON-COMPETING CONTINUATION	$248,769
2011	2011	CURATORS OF THE UNIVERSITY OF MISSOURI	310 Jesse Hall	Columbia	MO	65211	BOONE	USA	Biomedical Research and Research Training	001	8	6/7/2011	NON-COMPETING CONTINUATION	$24,877
														Subtotal = $273,646

Issue Date FY: 2010 ( Subtotal = $276,457 )
2010	2010	CURATORS OF THE UNIVERSITY OF MISSOURI	310 Jesse Hall	Columbia	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	7	4/12/2010	NON-COMPETING CONTINUATION	$276,457
														Subtotal = $276,457

Issue Date FY: 2009 ( Subtotal = $273,886 )
2009	2009	CURATORS OF THE UNIVERSITY OF MISSOURI	310 Jesse Hall	Columbia	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	6	4/20/2009	NON-COMPETING CONTINUATION	$273,886
														Subtotal = $273,886

Issue Date FY: 2008 ( Subtotal = $286,463 )
2008	2008	CURATORS OF THE UNIVERSITY OF MISSOURI	310 Jesse Hall	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	5	7/7/2008	COMPETING CONTINUATION	$286,463
														Subtotal = $286,463

Issue Date FY: 2005 ( Subtotal = $181,984 )
2005	2005	UNIVERSITY OF MISSOURI	310 JESSE HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	4	4/15/2005	NON-COMPETING CONTINUATION	$173,143
2005	2005	UNIVERSITY OF MISSOURI	310 JESSE HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	001	3	1/24/2005	SUPPLEMENT FOR EXPANSION	$8,841
														Subtotal = $181,984

Issue Date FY: 2004 ( Subtotal = $134,169 )
2004	2004	UNIVERSITY OF MISSOURI	310 JESSE HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	3	4/19/2004	NON-COMPETING CONTINUATION	$134,169
														Subtotal = $134,169

Issue Date FY: 2003 ( Subtotal = $134,169 )
2003	2003	UNIVERSITY OF MISSOURI	310 JESSE HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	2		NON-COMPETING CONTINUATION	$134,169
														Subtotal = $134,169

Issue Date FY: 2002 ( Subtotal = $107,335 )
2002	2002	UNIVERSITY OF MISSOURI	310 JESSE HALL	COLUMBIA	MO	65211	BOONE	USA	Biomedical Research and Research Training	000	1	5/3/2002	NEW	$107,335
														Subtotal = $107,335

Grand Total All Awards = $4,980,419

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Substrate Channeling and Communication in Proline Metabolic Enzymes

Award Number: R01GM065546

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: 05/05/2002

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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