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Spectroscopic Studies of Molybdoenzymes & Models

Award Number: R01GM057378
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: 06/01/1998
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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Spectroscopic Studies of Molybdoenzymes & Models - There exist fundamental gaps in the knowledge base regarding the final steps of molybdenum cofactor (Moco) biosynthesis and sulfuration, how the Mo methionine sulfoxide reductase utilizes the pyranopterin dithiolene component (MPT) of the cofactor in catalysis, and the role of non-MPT ligands in the catalytic cycles of dimethylsulfoxide reductase family enzymes. Our long-term goal is to understand geometric and electronic structure contributions to pyranopterin molybdenum enzyme reactivity and function in order to provide a positive impact on the quality of human health. Our primary objectives are to determine critical Moco maturation, transport and sulfuration steps, define the mechanism of MsrP and the role of the MPT in Msr mediated catalysis, and understand the electronic structure of key paramagnetic intermediates in DMSOR family enzymes using a combined spectroscopic approach augmented by detailed bonding, spectroscopic, and reaction coordinate calculations. The central hypothesis is that specific geometric and electronic structure modifications of protein- bound Moco define the unique reactions catalyzed. The rationale for this research is that a comprehensive understanding of Moco maturation and transport, the complex interplay between Mo the MPT in Msr catalysis, and the nature of paramagnetic DMSOR family intermediates will provide new insights into disease states and have a positive impact on human health. We will test our central hypothesis in order to accomplish the objectives of this proposal through the successful pursuit of three Specific Aims 1) Understand Moco maturation, transport, and sulfuration, 2) Determine electronic structure contributions to MsrP catalysis, 3) Determine the electronic and geometric structure of paramagnetic intermediates in DMSOR family enzymes. The proposed research is innovative in its approach because we have integrated structural, multicomponent spectroscopic, and computational investigations on models and enzymes to address critical questions concerning the final stages of Moco biosynthesis and sulfuration, Mo catalyzed repair mechanisms for oxidatively damaged proteins, and the synergistic interactions between MPT and amino acid ligation in pyranopterin Mo enzyme catalysis. This has led to new insight into long-standing questions in the molybdoenzyme field, effectively opening new horizons for future work in this area. The proposed research is significant since it will impact and advance our understanding of molybdate insertion and post-translational sulfuration processes, sulfur and Moco trafficking, molybdoenzyme mediated rescue of oxidatively damaged proteins, and the roles of amino acid and pyranopterin dithiolene ligands in molybdoenzyme catalysis.


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: 2025 ( Subtotal = $0 )
2025	2022	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	24	12/2/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $326,936 )
2022	2022	UNIVERSITY OF NEW MEXICO, THE	1700 LOMAS BLVD NE STE 2200	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	000	24	5/11/2022	NON-COMPETING CONTINUATION	$326,936
														Subtotal = $326,936

Issue Date FY: 2021 ( Subtotal = $327,297 )
2021	2021	UNIVERSITY OF NEW MEXICO, THE	1700 LOMAS BLVD NE STE 2200	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	000	23	6/8/2021	NON-COMPETING CONTINUATION	$327,297
														Subtotal = $327,297

Issue Date FY: 2020 ( Subtotal = $327,637 )
2020	2020	UNIVERSITY OF NEW MEXICO	1700 LOMAS BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	002	22	5/11/2020	NON-COMPETING CONTINUATION	$327,637
2020	2019	UNIVERSITY OF NEW MEXICO, THE	1700 LOMAS BLVD NE STE 2200	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	001	21	1/9/2020	COMPETING CONTINUATION	$126,940
2020	2018	UNIVERSITY OF NEW MEXICO, THE	1700 LOMAS BLVD NE STE 2200	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	000	20	1/9/2020	NON-COMPETING CONTINUATION	-$126,940
														Subtotal = $327,637

Issue Date FY: 2019 ( Subtotal = $300,799 )
2019	2019	UNIVERSITY OF NEW MEXICO	1700 LOMAS BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	001	21	9/3/2019	COMPETING CONTINUATION	$300,799
2019	2018	UNIVERSITY OF NEW MEXICO	1700 LOMAS BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	000	20	9/3/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $300,799

Issue Date FY: 2018 ( Subtotal = $319,649 )
2018	2018	UNIVERSITY OF NEW MEXICO	1700 LOMAS BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	000	20	7/25/2018	NON-COMPETING CONTINUATION	$319,649
														Subtotal = $319,649

Issue Date FY: 2017 ( Subtotal = $319,993 )
2017	2017	UNIVERSITY OF NEW MEXICO	1700 LOMAS BLVD NE	ALBUQUERQUE	NM	87106	BERNALILLO	USA	Biomedical Research and Research Training	000	19	8/1/2017	NON-COMPETING CONTINUATION	$319,993
														Subtotal = $319,993

Issue Date FY: 2016 ( Subtotal = $317,503 )
2016	2016	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	18	8/30/2016	NON-COMPETING CONTINUATION	$317,503
														Subtotal = $317,503

Issue Date FY: 2015 ( Subtotal = $275,972 )
2015	2015	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	001	17	7/27/2015	COMPETING CONTINUATION	$275,972
2015	2014	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	16	7/22/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $275,972

Issue Date FY: 2014 ( Subtotal = $317,100 )
2014	2014	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	16	5/22/2014	NON-COMPETING CONTINUATION	$317,100
														Subtotal = $317,100

Issue Date FY: 2013 ( Subtotal = $306,002 )
2013	2013	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	15	3/26/2013	NON-COMPETING CONTINUATION	$285,390
2013	2013	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	001	15	6/21/2013	NON-COMPETING CONTINUATION	$20,612
														Subtotal = $306,002

Issue Date FY: 2012 ( Subtotal = $302,042 )
2012	2012	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	14	3/15/2012	NON-COMPETING CONTINUATION	$302,042
														Subtotal = $302,042

Issue Date FY: 2011 ( Subtotal = $282,355 )
2011	2011	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	001	13	8/2/2011	COMPETING CONTINUATION	$282,355
2011	2010	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	12	8/1/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $282,355

Issue Date FY: 2010 ( Subtotal = $290,902 )
2010	2010	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	12	2/4/2010	NON-COMPETING CONTINUATION	$290,902
														Subtotal = $290,902

Issue Date FY: 2009 ( Subtotal = $293,840 )
2009	2009	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	001	11	5/1/2009	NON-COMPETING CONTINUATION	$29,384
2009	2009	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	11	2/9/2009	NON-COMPETING CONTINUATION	$264,456
														Subtotal = $293,840

Issue Date FY: 2008 ( Subtotal = $280,117 )
2008	2008	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	10	2/14/2008	NON-COMPETING CONTINUATION	$280,117
														Subtotal = $280,117

Issue Date FY: 2007 ( Subtotal = $277,200 )
2007	2007	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	9	1/29/2007	COMPETING CONTINUATION	$277,200
														Subtotal = $277,200

Issue Date FY: 2005 ( Subtotal = $251,865 )
2005	2005	UNIVERSITY OF NEW MEXICO (THE)	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	8	6/28/2005	NON-COMPETING CONTINUATION	$251,865
														Subtotal = $251,865

Issue Date FY: 2004 ( Subtotal = $251,865 )
2004	2004	UNIVERSITY OF NEW MEXICO (THE)	915 CAMINO DE SALUD NORTHEAST	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	7	5/21/2004	NON-COMPETING CONTINUATION	$251,865
														Subtotal = $251,865

Issue Date FY: 2003 ( Subtotal = $261,473 )
2003	2003	UNIVERSITY OF NEW MEXICO (THE)	915 CAMINO DE SALUD NORTHEAST	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	6	5/23/2003	NON-COMPETING CONTINUATION	$261,473
														Subtotal = $261,473

Issue Date FY: 2002 ( Subtotal = $273,772 )
2002	2002	UNIVERSITY OF NEW MEXICO (THE)	915 CAMINO DE SALUD NORTHEAST	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Biomedical Research and Research Training	000	5	5/13/2002	COMPETING CONTINUATION	$273,772
														Subtotal = $273,772

Issue Date FY: 2001 ( Subtotal = $143,534 ) (Continued on the next page)
Grand Total All Awards = $6,510,648

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Spectroscopic Studies of Molybdoenzymes & Models

Award Number: R01GM057378

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: 06/01/1998

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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