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Young, Tessa R., Deery, Evelyne, Foster, Andrew W., Martini, Maria Alessandra, Osman, Deenah, Warren, Martin J. 
ORCID: https://orcid.org/0000-0002-6028-6456 and Robinson, Nigel J.
(2023)
Two distinct thermodynamic gradients for cellular metalation of vitamin B12.
JACS Au, 3 (5).
pp. 1472-1483.
ISSN 2691-3704
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Abstract
The acquisition of CoIIby the corrin component of vitamin B12follows one of two distinct pathways, referred to as early or late CoIIinsertion. The late insertion pathway exploits a CoIImetallochaperone (CobW) from the COG0523 family of G3E GTPases, while the early insertion pathway does not. This provides an opportunity to contrast the thermodynamics of metalation in a metallochaperone-requiring and a metallochaperone-independent pathway. In the metallochaperone-independent route, sirohydrochlorin (SHC) associates with the CbiK chelatase to form CoII-SHC. CoII-buffered enzymatic assays indicate that SHC binding enhances the thermodynamic gradient for CoIItransfer from the cytosol to CbiK. In the metallochaperone-dependent pathway, hydrogenobyrinic acid a,c-diamide (HBAD) associates with the CobNST chelatase to form CoII-HBAD. Here, CoII-buffered enzymatic assays indicate that CoIItransfer from the cytosol to HBAD-CobNST must somehow traverse a highly unfavorable thermodynamic gradient for CoIIbinding. Notably, there is a favorable gradient for CoIItransfer from the cytosol to the MgIIGTP-CobW metallochaperone, but further transfer of CoIIfrom the GTP-bound metallochaperone to the HBAD-CobNST chelatase complex is thermodynamically unfavorable. However, after nucleotide hydrolysis, CoIItransfer from the chaperone to the chelatase complex is calculated to become favorable. These data reveal that the CobW metallochaperone can overcome an unfavorable thermodynamic gradient for CoIItransfer from the cytosol to the chelatase by coupling this process to GTP hydrolysis.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by a Royal Commission for the Exhibition of 1851 Research Fellowship (T.R.Y.), Royal Society Industrial Fellowship INF\R2\180062 (M.J.W.), and Biotechnology and Biological Sciences Research Council awards BB/V006002/1, BB/W015749/1, BB/S009787/1, BB/S002197/1, and BBS/E/F/000PR10346. |
| Uncontrolled Keywords: | bioinorganic chemistry,chelatase,gtpase,metalation,metallochaperone,metalloprotein,vitamin b,analytical chemistry,chemistry (miscellaneous),physical and theoretical chemistry,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1600/1602 |
| 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: | 24 Oct 2024 09:30 |
| Last Modified: | 24 Oct 2024 09:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97175 |
| DOI: | 10.1021/jacsau.3c00119 |
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