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Publication Abstract from PubMed

Dynamics is an essential process to drive an enzyme to perform a function. When a protein sequence encodes for its three-dimensional structure and hence its function, it essentially defines the intrinsic dynamics of the molecule. The static X-ray crystal structure was thought to shed little insight into the molecule's dynamics until the recently available tool "Ensemble refinement" (ER). Here, we report the structure-function-dynamics of PanPL, an alginate-specific, endolytic, allosteric polysaccharide lyase belonging to the PL-5 family from Pandoraea apista. The crystal structures determined in apo and tetra-ManA bound forms reveal that the PanPL maintains a closed state with an N-terminal loop lid (N-loop-lid) arched over the active site. The B-factor analyses and ER congruently reveal how pH influences the functionally relevant atomic fluctuations at the N-loop-lid. The ER unveils enhanced fluctuations at the N-loop-lid upon substrate binding. The normal-mode analysis finds that the functional states are confined. The 1 mus simulation study suggests the existence of a hidden open state. The longer N-loop-lid selects a mechanism to adopt a closed state and undergo fluctuations to facilitate the substrate binding. Here, our work demonstrates the distinct modes of dynamics; both intrinsic and substrate-induced conformational changes are vital for enzyme functioning and allostery.

Distinct Modes of Hidden Structural Dynamics in the Functioning of an Allosteric Polysaccharide Lyase.,Dash P, Acharya R ACS Cent Sci. 2022 Jul 27;8(7):933-947. doi: 10.1021/acscentsci.2c00277. Epub , 2022 Jul 6. PMID:35912344^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.