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Biosynthetic Models of Heteronuclear Metalloenzymes in Multi-electron Processes

Award Number: R01GM062211
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract The overall goal of the project is to achieve holistic understanding of structure and function of heteronuclear metalloenzymes involved in multi-electron redox processes, which are more difficult to study than homonuclear enzymes, and to address important scientific issues in the fields of respiration and the global nitrogen and sulfur cycles. Specifically, we seek to investigate why a heme-nonheme Fe center in nitric oxide reductase (NOR) is effective at 2e- reduction of NO, allowing N-N bond formation, whereas a heme-Cu center in heme-Cu oxidase (HCO) is proficient at 4e- reduction of O2, enabling O-O bond cleavage, while both a different heme-Cu center in sulfite reductase from W. succinogenes (SiRA) and a heme-Fe4S4 center in assimilatory sulfite reductases (SiR) are efficient at 6e- reduction of sulfite, promoting S-O bond cleavage. To achieve this goal, the proposal is based on a scientific premise that developing a novel biosynthetic approach using stable, easy-to-produce, and well-characterized heme proteins as scaffolds for making structural and functional models of HCO, NOR, SiRA and SiR can overcome critical methodological barriers to progress in the field. We will use the biosynthetic models to 1) Understand how a heme-Cu center can exhibit either HCO or SiR activity, 2) elucidate structural features responsible for catalytic activity and substrate binding affinity of SiR, 3) clarify the roles of Tyr in HCO and SiR activities, and 4) investigate the roles of heme cofactors in HCO, NOR and SiR activities. To ensure scientific rigor, we will use activity as guidance for our project design and spectroscopic, crystallographic and computational techniques to characterize our models. Achieving the above goals will result in deeper understanding of the structure and function of HCO, NOR, SiRA and SiR that may be very difficult to achieve by studying the native enzymes alone. The ability to place different heteronuclear metal centers into the same protein scaffold offers insight into similarities and differences between the four heteronuclear metalloenzymes. In doing so, the project will advance the knowledge of metalloprotein structure, function, and design in general, as the guiding principles obtained from these studies will be applicable to a broad range of metalloenzymes important for human health.


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: 2023 ( Subtotal = -$19,854 )
2023	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	000	20	10/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$19,854
														Subtotal = -$19,854

Issue Date FY: 2022 ( Subtotal = $16,420 )
2022	2021	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	003	19	7/27/2022	NON-COMPETING CONTINUATION	-$1
2022	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	001	20	4/4/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$307,791
2022	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Biomedical Research and Research Training	004	20	7/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$19,854
2022	2021	UNIVERSITY OF ILLINOIS	352 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	19	3/31/2022	NON-COMPETING CONTINUATION	-$291,371
2022	2020	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	002	18	7/27/2022	NON-COMPETING CONTINUATION	-$19,853
														Subtotal = $16,420

Issue Date FY: 2021 ( Subtotal = $291,372 )
2021	2021	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	19	3/30/2021	NON-COMPETING CONTINUATION	$291,372
2021	2021	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	19	6/1/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $291,372

Issue Date FY: 2020 ( Subtotal = $292,124 )
2020	2020	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	18	3/6/2020	NON-COMPETING CONTINUATION	$292,124
														Subtotal = $292,124

Issue Date FY: 2019 ( Subtotal = $292,854 )
2019	2019	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	17	3/29/2019	COMPETING CONTINUATION	$292,854
2019	2018	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	16	3/26/2019	NON-COMPETING CONTINUATION	$0
2019	2018	UNIVERSITY OF ILLINOIS	364 HENRY ADMINISTRATION BLDG	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	002	16	7/23/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $292,854

Issue Date FY: 2018 ( Subtotal = $309,019 )
2018	2018	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	16	1/12/2018	NON-COMPETING CONTINUATION	$278,117
2018	2018	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	16	5/21/2018	NON-COMPETING CONTINUATION	$30,902
														Subtotal = $309,019

Issue Date FY: 2017 ( Subtotal = $309,258 )
2017	2017	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	000	15	1/4/2017	NON-COMPETING CONTINUATION	$278,332
2017	2017	UNIVERSITY OF ILLINOIS	506 S WRIGHT ST STE 364	URBANA	IL	61801	CHAMPAIGN	USA	Biomedical Research and Research Training	001	15	6/6/2017	NON-COMPETING CONTINUATION	$30,926
														Subtotal = $309,258

Issue Date FY: 2016 ( Subtotal = $305,363 )
2016	2016	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	001	14	2/24/2016	NON-COMPETING CONTINUATION	$30,537
2016	2016	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	14	1/13/2016	NON-COMPETING CONTINUATION	$274,826
														Subtotal = $305,363

Issue Date FY: 2015 ( Subtotal = $299,400 )
2015	2015	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	13	2/9/2015	COMPETING CONTINUATION	$299,400
														Subtotal = $299,400

Issue Date FY: 2013 ( Subtotal = $282,642 )
2013	2013	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	12	8/21/2013	NON-COMPETING CONTINUATION	$282,642
														Subtotal = $282,642

Issue Date FY: 2012 ( Subtotal = $292,894 )
2012	2012	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	11	8/16/2012	NON-COMPETING CONTINUATION	$292,894
														Subtotal = $292,894

Issue Date FY: 2011 ( Subtotal = $292,894 )
2011	2011	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	10	8/25/2011	NON-COMPETING CONTINUATION	$292,894
														Subtotal = $292,894

Issue Date FY: 2010 ( Subtotal = $295,095 )
2010	2010	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	9	8/16/2010	COMPETING CONTINUATION	$295,095
														Subtotal = $295,095

Issue Date FY: 2009 ( Subtotal = $241,268 )
2009	2009	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	8	8/31/2009	NON-COMPETING CONTINUATION	$241,268
														Subtotal = $241,268

Issue Date FY: 2008 ( Subtotal = $241,268 )
2008	2008	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	7	8/18/2008	NON-COMPETING CONTINUATION	$241,268
														Subtotal = $241,268

Issue Date FY: 2007 ( Subtotal = $241,268 )
2007	2007	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	6	8/30/2007	NON-COMPETING CONTINUATION	$241,268
														Subtotal = $241,268

Issue Date FY: 2006 ( Subtotal = $289,075 )
2006	2006	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	5	9/22/2006	COMPETING CONTINUATION	$289,075
														Subtotal = $289,075

Issue Date FY: 2004 ( Subtotal = $213,930 )
2004	2004	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	4	3/22/2004	NON-COMPETING CONTINUATION	$213,930
														Subtotal = $213,930

Issue Date FY: 2003 ( Subtotal = $214,171 )
2003	2003	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	3		NON-COMPETING CONTINUATION	$214,171
														Subtotal = $214,171

Issue Date FY: 2002 ( Subtotal = $214,406 )
2002	2002	UNIVERSITY OF ILLINOIS BOARD OF TRUSTEES	109 COBLE HALL, 801 S WRIGHT S	CHAMPAIGN	IL	61820	CHAMPAIGN	USA	Biomedical Research and Research Training	000	2	3/22/2002	NON-COMPETING CONTINUATION	$214,406
														Subtotal = $214,406

Grand Total All Awards = $5,129,501

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Biosynthetic Models of Heteronuclear Metalloenzymes in Multi-electron Processes

Award Number: R01GM062211

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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