PIPages
Labs

Gayan Wijeratne

University of Alabama, AL·Chemistry

Heme enzymes are proteins built around heme, an iron-containing group. They drive many essential reactions in the human body.

Fields

Chemistry

Biochemistry

Topics

heme enzymes

bioinorganic chemistry

coordination chemistry

Grants
1 known grant, through Apr 2029

What they work on

  1. Synthesize heme-nitrogen oxide model complexes with systematically varied ligands in the primary and secondary coordination spheres, to find which features of the heme center control the geometry and electronic structure of these intermediates.
  2. Evaluate how readily mid-valent iron(III) heme species such as peroxynitrite and hyponitrite complexes form, how stable they are, and how they react in biologically relevant reactions, to build structure-activity relationships.
  3. Trap short-lived intermediates of nitrogen oxide interconversion at cryogenic temperatures and identify them using combined spectroscopic and theoretical methods.
  4. Map the reaction landscapes of synthetic heme mimics through detailed thermodynamic and kinetic studies, information that is very hard to obtain from the enzymes themselves.

More about the research

They also take part in disease processes, including major neurodegenerative and autoimmune conditions and cancer. Researchers have tried to block these enzymes with selective drugs, but how most of them actually work is still poorly understood. That makes it hard to design inhibitors based on their mechanisms. Most mechanistic studies have looked at high-valent heme species, in which the iron is highly oxidized. Mid-valent species, with iron in the +3 state bound to groups such as superoxo, peroxo, hydroperoxo, peroxynitrite or hyponitrite, remain much less studied. Yet these species are key oxidants or intermediates in enzymes that matter for health.

Why it matters

Nitrogen oxide reactions catalyzed by heme enzymes underlie a variety of disease conditions. Clearer mechanisms could improve understanding of how these diseases begin and progress. They could also support efforts to design drug candidates that target heme enzymes with greater effectiveness and specificity.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Mechanistic Investigation into Nitric Oxide Interconversion Pathways of Heme Enzymes using Synthetic Mimics

NIH · Jun 2024 – Apr 2029

Closest labs

John Gilbertson

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Develop a class of ditopic receptors, metal complexes with two hydrogen-bond-donating sites near the metal, that capture and reduce nitrite and nitrate (NOx-), built on the redox-active pyridinediimine (PDI) ligand.

Rupal Gupta

College of Staten Island CUNY, NY·Biochemistry

Determine how 3-His iron-binding sites, an unusual alternative to the common 2-His-1-carboxylate motif, change the reaction mechanisms of non-heme iron enzymes that cut aromatic rings, using biochemical and spectroscopic methods.

Claude Goldsmith

Brown University, RI·Engineering

Measure branching fractions, the share of a reaction going to each possible product, for key NOx-related reactions in ammonia combustion, using shock tube experiments.

The school

University of Alabama: 22 labs on PI Pages, $221M a year on research, 235 research doctorates a year.

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