Hedison, Tobias M and Shenoy, Rajesh T and Iorgu, Andreea I and Heyes, Derren J and Fisher, Karl and Wright, Gareth SA and Hay, Sam and Eady, Robert R and Antonyuk, Svetlana V and Hasnain, S Samar and Scrutton, Nigel S (2019) Unexpected Roles of a Tether Harboring a Tyrosine Gatekeeper Residue in Modular Nitrite Reductase Catalysis. ACS Catalysis, 9 (7). pp. 6087-6099. DOI https://doi.org/10.1021/acscatal.9b01266
Hedison, Tobias M and Shenoy, Rajesh T and Iorgu, Andreea I and Heyes, Derren J and Fisher, Karl and Wright, Gareth SA and Hay, Sam and Eady, Robert R and Antonyuk, Svetlana V and Hasnain, S Samar and Scrutton, Nigel S (2019) Unexpected Roles of a Tether Harboring a Tyrosine Gatekeeper Residue in Modular Nitrite Reductase Catalysis. ACS Catalysis, 9 (7). pp. 6087-6099. DOI https://doi.org/10.1021/acscatal.9b01266
Hedison, Tobias M and Shenoy, Rajesh T and Iorgu, Andreea I and Heyes, Derren J and Fisher, Karl and Wright, Gareth SA and Hay, Sam and Eady, Robert R and Antonyuk, Svetlana V and Hasnain, S Samar and Scrutton, Nigel S (2019) Unexpected Roles of a Tether Harboring a Tyrosine Gatekeeper Residue in Modular Nitrite Reductase Catalysis. ACS Catalysis, 9 (7). pp. 6087-6099. DOI https://doi.org/10.1021/acscatal.9b01266
Abstract
It is generally assumed that tethering enhances rates of electron harvesting and delivery to active sites in multidomain enzymes by proximity and sampling mechanisms. Here, we explore this idea in a tethered 3-domain, trimeric copper-containing nitrite reductase. By reverse engineering, we find that tethering does not enhance the rate of electron delivery from its pendant cytochrome c to the catalytic copper-containing core. Using a linker that harbors a gatekeeper tyrosine in a nitrite access channel, the tethered haem domain enables catalysis by other mechanisms. Tethering communicates the redox state of the haem to the distant T2Cu center that helps initiate substrate binding for catalysis. It also tunes copper reduction potentials, suppresses reductive enzyme inactivation, enhances enzyme affinity for substrate, and promotes intercopper electron transfer. Tethering has multiple unanticipated beneficial roles, the combination of which fine-tunes function beyond simplistic mechanisms expected from proximity and restrictive sampling models.
Item Type: | Article |
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Uncontrolled Keywords: | copper nitrite reductase; tethering; enzyme catalysis; electron transfer; modular enzyme architecture; intraprotein electron transfer; interprotein electron transfer; protein dynamics |
Divisions: | Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 28 Aug 2025 18:42 |
Last Modified: | 28 Aug 2025 18:43 |
URI: | http://repository.essex.ac.uk/id/eprint/34757 |
Available files
Filename: Unexpected Roles of a Tether Harboring a Tyrosine Gatekeeper Residue in Modular Nitrite Reductase Catalysis.pdf
Licence: Creative Commons: Attribution 4.0