Biophysical Society Thematic Meeting

New Biological Frontiers Illuminated by Molecular Sensors and Actuators

Poster Abstracts

9-POS

Board 9

Globin Nitrito Heme Fe-O-N=O/ 2-Nitrovinyl Species: Impications for Myoglobin Helices

Dynamics

Evangelos Daskalakis

, Neofyta Ioannou

, Eftychia Pinakoulaki

Cyprus University of Technology, LImassol, Cyprus,

University of Cyprus, Nicosia, Nikosia,

Cyprus.

Nitrite acts as a ‘pool’ for the NO signaling molecule under hypoxic and anoxic conditions, when

NO synthase activity is impaired. This is supported by the growing number of metallo-proteins

that are reported to be able to reduce nitrite to nitric oxide in mammals. Nitrates and nitrites have

been viewed as storage pools supporting NO signaling during metabolic stress and their bio

activation, involves both enzymatic and non-enzymatic reactions in tissues and blood. Nitrites

react with heme proteins leading to several heme Fe adducts and the catalyzed reaction pathways

play a vital role for deoxy-hemoglobin and deoxy-myoglobin (Mb) dependent nitrite reduction.

Structural information based on X-ray crystallography of the unusual Mb-nitrite interactions has

been reported, and mechanisms for nitrite conversion to NO have been proposed. A detailed

characterization of the structures and bonding of the bound nitrite and its interaction with the

protein environment in its natural environment rather than in crystals, however, is lacking. The

description of biological activity in heme proteins responsible for activating small molecules

requires identification of ligand movement into the metal and non-metal binding sites at the

atomistic level. Mechanisms of nitrite reductase activity in globins are difficult to verify without

the dynamical aspects of the ligand binding. Computational Modeling for the NO

2 -

adducts of

heme proteins is becoming increasingly important. The conditions under which the nitrito heme

Fe-O-N=O/ 2-nitrovinyl species is generated in Mb and interacts with the protein matrix are

identified at the atomistic level employing Molecular Dynamics Simulations and Density

Functional Theory Calculations. Helices movement and flexibility in Mb are strongly affected

upon the nitrite binding, altering also the Mb spectroscopic characteristics. We correlate these

theoretical findings with results from resonance Raman Spectroscopy.