CATALYTIC MECHANISMS AND PROPERTIES OF HEME PROTEINS

Project: Research project

Project Details

Description

DESCRIPTION: This is a proposal that describes studies that focus primarily
on the proteins Nitric Oxide Synthase (NOS) and Cytochrome c Oxidase (CCO),
and with smaller efforts being devoted to Heme Oxygenase (HO) and the
Fe-bleomycin complex. The theme of this work is to determine the properties
of catalytic intermediates involving oxygen activation and utilization and
all four subjects of this proposal produce such intermediates. Raman and
optical spectroscopies will be used in these studies. NOS is the enzyme
that generates nitric oxide from arginine and this proposal involves
expanding significant preliminary studies in order to mechanistically
characterize how the enzyme generates and controls NO. NO is, of course and
important physiological molecule, playing roles in neurotransmission,
vasodilation and cytotoxicity. CCO is the terminal enzyme in the electron
transfer chain and it plays a dual role, reducing molecular oxygen to water
and translocating protons across the inner mitochondrial membrane. The goal
for this enzyme is to continue the body of significant preliminary work on
this enzyme that has been produced in the PI's laboratory in order to
determine structural features of the intermediates in the catalytic cycle
for the mammalian enzyme and to determine the kinetics associated with these
intermediates. HO is the rate-limiting enzyme of the microsomal heme
degradation pathway and its role is to bind Iron-protoporphyrinIX and
convert it to biliverdin- IX(alpha). Bleomycin is a glycopeptide antibiotic
that exhibits antitumor activity towards neoplasms. The mechanism of this
drugs effect is unknown, but evidence suggest that it involves activated
oxygen intermediates.
StatusFinished
Effective start/end date1/1/9712/31/97

Funding

  • National Institute of General Medical Sciences

ASJC

  • Catalysis

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