English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

S-adenosylhomocysteine hydrolase (SAHH), a cellular enzyme that plays a keyrole in methylation reactions including those required for maturation of viralmRNA, is an important drug target in the discovery of antiviral agents. Whiletargeting the active site is a straightforward strategy of enzyme inhibition,evidences of allosteric modulation of active site in many enzymes underscorethe molecular origin of signal transduction. Information of co-evolvingsequences in SAHH family and the key residues for functional dynamics that canbe identified using native topology of the enzyme provide glimpses into how theallosteric signaling network, dispersed over the molecular structure,coordinates intra- and inter-subunit conformational dynamics. To study the linkbetween the allosteric communication and functional dynamics of SAHHs, weperformed Brownian dynamics simulations by building a coarse-grained modelbased on the holo and ligand-bound structures. The simulations ofligand-induced transition revealed that the signal of intra-subunit closuredynamics is transmitted to form inter-subunit contacts, which in turn invoke aprecise alignment of active site, followed by the dimer-dimer rotation thatcompacts the whole tetrameric structure. Further analyses of SAHH dynamicsassociated with ligand binding provided evidence of both induced fit andpopulation shift mechanisms, and also showed that the transition state ensembleis akin to the ligand-bound state. Besides the formation of enzyme-ligandcontacts at the active site, the allosteric couplings from the residues distalto the active site is vital to the enzymatic function.

Link between allosteric signal transduction and functional dynamics in a multi-subunit enzyme: S-adenosylhomocysteine hydrolase