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Pérez-Castaño, Ricardo, Aranda, Juan, Widner, Florian J., Kieninger, Christoph, Deery, Evelyne, Warren, Martin J. 
ORCID: https://orcid.org/0000-0002-6028-6456, Orozco, Modesto, Elías-Arnanz, Montserrat, Padmanabhan, S. and Kräutler, Bernhard
(2024)
The rhodium analogue of coenzyme B12 as an anti-photoregulatory ligand inhibiting bacterial CarH photoreceptors.
Angewandte Chemie - International Edition, 63 (18).
ISSN 1433-7851
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Abstract
Coenzyme B12 (AdoCbl; 5′-deoxy-5′-adenosylcobalamin), the quintessential biological organometallic radical catalyst, has a formerly unanticipated, yet extensive, role in photoregulation in bacteria. The light-responsive cobalt-corrin AdoCbl performs this nonenzymatic role by facilitating the assembly of CarH photoreceptors into DNA-binding tetramers in the dark, suppressing gene expression. Conversely, exposure to light triggers the decomposition of this AdoCbl-bound complex by a still elusive photochemical mechanism, activating gene expression. Here, we have examined AdoRhbl, the non-natural rhodium analogue of AdoCbl, as a photostable isostructural surrogate for AdoCbl. We show that AdoRhbl closely emulates AdoCbl in its uptake by bacterial cells and structural functionality as a regulatory ligand for CarH tetramerization, DNA binding, and repressor activity. Remarkably, we find AdoRhbl is photostable even when bound “base-off/His-on” to CarH in vitro and in vivo. Thus, AdoRhbl, an antivitamin B12, also represents an unprecedented anti-photoregulatory ligand, opening a pathway to precisely target biomimetic inhibition of AdoCbl-based photoregulation, with new possibilities for selective antibacterial applications. Computational biomolecular analysis of AdoRhbl binding to CarH yields detailed structural insights into this complex, which suggest that the adenosyl group of photoexcited AdoCbl bound to CarH may specifically undergo a concerted non-radical syn-1,2-elimination mechanism, an aspect not previously considered for this photoreceptor.
| Item Type: | Article |
|---|---|
| Additional Information: | Data Availability Statement: The data that support the findings of this study are available in the supplementary material of this article. Funding Information: This work was funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”, grants PGC2018‐094635‐B‐C21 and PID2021‐123336NB‐C21 to M.E.‐A. and Ph.D. fellowship to R.P.‐C.; PGC2018‐094635‐B‐C22 and PID2021‐123336NB‐C22 to S.P; PID2021‐122478NB‐100 to M.O.; Juan de la Cierva investigator grant to J.A; Severo Ochoa Institutional Award to IRB‐Barcelona; Fundación Séneca‐Spain grants 20992/PI/18 and 21939/PI/22 to M.E.‐A.; Catalan SGR, European Union BioExcel‐3 project 1010932290 (European Union's Horizon 2020 research and innovation program), Instituto Nacional de Bioinformática, Biomolecular and Bioinformatics Resources Platform (ISCIII PT 13/0001/0030) to MO; Austrian Science Fund (projects P‐28892 and P‐33059) to BK; and the Biotechnology and Biological Sciences Research Council (BBSRC), project grant BB/X001946/1, and BBSRC Institute Strategic Programme Food Innovation and Health BB/R012512/1, project BBS/E/F/000PR10346 to MJW. |
| Uncontrolled Keywords: | antivitamin b,cobalamin,photoinhibitor,photoreceptor,rhodium,catalysis,chemistry(all) ,/dk/atira/pure/subjectarea/asjc/1500/1503 |
| Faculty \ School: | Faculty of Science |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 23 Oct 2024 16:30 |
| Last Modified: | 16 Dec 2024 01:43 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97167 |
| DOI: | 10.1002/anie.202401626 |
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