Zhang, HanHanZhangLi, YuchenYuchenLiNie, JingleiJingleiNieRen, JieJieRenZeng, An-PingAn-PingZeng2021-01-142021-01-142020-12Communications Biology 3 (1): 756 (2020-12)http://hdl.handle.net/11420/8445Molecular 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.en2399-364220201Springer Naturehttps://creativecommons.org/licenses/by/4.0/TechnikJournal Article10.15480/882.351810.1038/s42003-020-01401-610.15480/882.351833311647Journal Article