Calculating metalation in cells reveals CobW acquires CoII for vitamin B12 biosynthesis while related proteins prefer ZnII

TR Young, MA Martini, AW Foster, A Glasfeld… - Nature …, 2021 - nature.com
Protein metal-occupancy (metalation) in vivo has been elusive. To address this challenge,
the available free energies of metals have recently been determined from the responses of
metal sensors. Here, we use these free energy values to develop a metalation-calculator
which accounts for inter-metal competition and changing metal-availabilities inside cells. We
use the calculator to understand the function and mechanism of GTPase CobW, a predicted
CoII-chaperone for vitamin B12. Upon binding nucleotide (GTP) and MgII, CobW assembles …

Calculating metalation in cells reveals CobW acquires CoII for vitamin B12 biosynthesis upon binding nucleotide

TR Young, MA Martini, D Osman, RJ Morton, E Deery… - BioRxiv, 2020 - biorxiv.org
Protein metal-occupancy (metalation) in vivo has been elusive. Here we develop a
metalation-calculator which accounts for inter-metal competition and changing metal-
availabilities inside cells. The calculations are based on available free-energies of metals
determined from the responses of metal sensors. We use the calculator to understand the
function and mechanism of CobW, a predicted CoII-chaperone for vitamin B12. CobW is
calculated to acquire negligible metal alone: But, upon binding nucleotide (GTP) and MgII …
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