7WXP

Crystal Structure of PL-5 family polysaccharide lyase PanPL-H172A mutant from Pandoraea apista in ManA bound form

Summary for 7WXP

• Entry DOI: 10.2210/pdb7wxp/pdb
• Descriptor: poly(beta-D-mannuronate) lyase, beta-D-mannopyranuronic acid-(1-4)-beta-D-mannopyranuronic acid (3 entities in total)
• Functional Keywords: pl-5 polysaccharide lyase panpl-h172a substrate (mana) bound form, lyase, pandoraea apista
• Biological source: Pandoraea apista
• Total number of polymer chains: 1
• Total formula weight: 40956.04

Authors

Dash, P.,Acharya, R. (deposition date: 2022-02-15, release date: 2022-08-10, Last modification date: 2023-11-29)

Primary citation

Dash, P.,Acharya, R.
Distinct Modes of Hidden Structural Dynamics in the Functioning of an Allosteric Polysaccharide Lyase.
Acs Cent.Sci., 8:933-947, 2022

PubMed Abstract: 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 . 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 μs 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.

PubMed: 35912344
DOI: 10.1021/acscentsci.2c00277

Experimental method

X-RAY DIFFRACTION (2.2 Å)