Heme edge reactivity towards sulfur- and oxygen-based stress agents
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
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.
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.
• 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).