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Structure-based dynamic analysis of the glycine cleavage system suggests key residues for control of a key reaction step
Citation Link: https://doi.org/10.15480/882.3518
Publikationstyp
Journal Article
Publikationsdatum
2020-12
Sprache
English
TORE-URI
Enthalten in
Volume
3
Issue
1
Article Number
756
Citation
Communications Biology 3 (1): 756 (2020-12)
Publisher DOI
Scopus ID
2-s2.0-85097493734
PubMed ID
33311647
Publisher
Springer Nature
Molecular shuttles play decisive roles in many multi-enzyme systems such as the glycine cleavage system (GCS) for one-carbon (C1) metabolism. In GCS, a lipoate swinging arm containing an aminomethyl moiety is attached to protein H and serves as a molecular shuttle among different proteins. Protection of the aminomethyl moiety in a cavity of protein H and its release induced by protein T are key processes but barely understood. Here, we present a detailed structure-based dynamic analysis of the induced release of the lipoate arm of protein H. Based on molecular dynamics simulations of interactions between proteins H and T, four major steps of the release process showing significantly different energy barriers and time scales can be distinguished. Mutations of a key residue, Ser-67 in protein H, led to a bidirectional tuning of the release process. This work opens ways to target C1 metabolism in biomedicine and the utilization of formate and CO2 for biosynthesis.
DDC Class
600: Technik
Funding Organisations
More Funding Information
This work was financially supported by the Beijing Advanced Innovation Center for Soft Matter Science and Engineering and by the Deutsche Forschungsgemeinschaft (DFG) through the project ZE 542/12-1 within the priority program SPP 1934.