Heme edge
reactivity towards sulfur- and oxygen-based stress agents
HERSOSA
PN-III-P1-1.1-PD-2021-0279
PD 101
Contracting
authority: Executive Unit for Financing Higher
Education, Research, Development and Innovation (UEFISCDI)
Implementation
period: 01/04/2022 - 31/03/2024
Budget:
250.000 RON
Project
director: Dr. Eng. Adrian M.V.
Brânzanic
Mentor:
Prof. Dr. Radu-Silaghi
Dumitrescu
Abstract
The
project aims to explore, through means of molecular modelling
methods, the formation edge-derived heme species in the active site of sulfite reductase. The enzyme was previously shown to use a
modified version a heme, namely siroheme, in order to avoid electron transfer
through inefficient routes. It was hypothesised that,
beside providing a faster route for the transferred
electrons required by catalysis, siroheme would also hinder the formation of
edge-derived species, such as sulfheme and hydroxyheme, that are known to
drastically affect the Fe atoms substrate binding affinity and that can cause porhyrin cleavage. Here we intend to prove that the special
conditions provided by the sulfite reductase active
site environment could lead to the formation edge-derived hemes
through previously unknown mechanisms.
Project Goals
Can
anionic heme radicals cause the formation of heme derived compounds in the
presence of S- and/or solvent molecules? Beside charge transfer optimisation, can the SiR blockade also inhibit undesired
side-reactions, or are these reactions impossible even in the absence of this
blockade? This is the core problem to
which we aim to provide an answer.
Phase I
•
DFT calculations on the sulfite reductase reaction
mechanism to better understand the nature of the possible intermediates present
and that have the potential to react with the porphyrin edge of the active
site.
•
Calculation of the most favorable electronic transfer routes in the synthetic
version (i.e. heme-cuban) of the active site.
•
Processing and preparing these results for publication.
•
Preparation of the QM/MM system of sulfite reductase
enzyme.
•
Parameterization of the active site of the sulfite reductase
enzyme.
•
Performing QM/MM calculations on the inactive version (i.e. with phosphate
bound to iron heme).
Useful
links:
https://www.brainmap.ro/adrian-branzanic
https://scholar.google.com/citations?view_op=list_works&hl=en&user=nEo0zQ0AAAAJ
https://www.researchgate.net/profile/Adrian-Branzanic