Abstract

The copper amine oxidase from bovine plasma has recently been found to contain 2,4,5-trihydroxyphenylalanine (topa) as the active site, redox cofactor. This discovery opens up many new avenues of research.
Specific aims for the projected granting period include: (1) Establishing the generality of topa as a redox cofactor in copper amine oxidases from a variety of sources (bacteria, yeast and mammalian tissue); (2) Determining the sequences of topa containing peptides, to ascertain the presence and nature of a consensus sequence; (3) Identifying the DNA sequence encoding the topa cofactor; (4) Establishing the pathway of topa biogenesis; (5) Elucidating the physical and chemical properties of topa model compounds; and (6) Pursuing the reactivity and catalytic properties of topa at the active site of bovine plasma amine oxidase.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM039296-05
Application #
3296146
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1988-02-01
Project End
1996-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Evans 3rd, Robert L; Latham, John A; Klinman, Judith P et al. (2016) (1)H, (13)C, and (15)N resonance assignments and secondary structure information for Methylobacterium extorquens PqqD and the complex of PqqD with PqqA. Biomol NMR Assign 10:385-9
Kulik, Heather J; Zhang, Jianyu; Klinman, Judith P et al. (2016) How Large Should the QM Region Be in QM/MM Calculations? The Case of Catechol O-Methyltransferase. J Phys Chem B 120:11381-11394
Barr, Ian; Latham, John A; Iavarone, Anthony T et al. (2016) Demonstration That the Radical S-Adenosylmethionine (SAM) Enzyme PqqE Catalyzes de Novo Carbon-Carbon Cross-linking within a Peptide Substrate PqqA in the Presence of the Peptide Chaperone PqqD. J Biol Chem 291:8877-84
Zhang, Jianyu; Klinman, Judith P (2016) Convergent Mechanistic Features between the Structurally Diverse N- and O-Methyltransferases: Glycine N-Methyltransferase and Catechol O-Methyltransferase. J Am Chem Soc 138:9158-65
Latham, John A; Iavarone, Anthony T; Barr, Ian et al. (2015) PqqD is a novel peptide chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE in the pyrroloquinoline quinone biosynthetic pathway. J Biol Chem 290:12908-18
Zhang, Jianyu; Kulik, Heather J; Martinez, Todd J et al. (2015) Mediation of donor-acceptor distance in an enzymatic methyl transfer reaction. Proc Natl Acad Sci U S A 112:7954-9
Zhang, Jianyu; Klinman, Judith P (2015) High-performance liquid chromatography separation of the (S,S)- and (R,S)-forms of S-adenosyl-L-methionine. Anal Biochem 476:81-3
Klinman, Judith P; Bonnot, Florence (2014) Intrigues and intricacies of the biosynthetic pathways for the enzymatic quinocofactors: PQQ, TTQ, CTQ, TPQ, and LTQ. Chem Rev 114:4343-65
Johnson, Bryan J; Yukl, Erik T; Klema, Valerie J et al. (2013) Structural snapshots from the oxidative half-reaction of a copper amine oxidase: implications for O2 activation. J Biol Chem 288:28409-17
Arnison, Paul G; Bibb, Mervyn J; Bierbaum, Gabriele et al. (2013) Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 30:108-60

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