Constant pH Accelerated Molecular Dynamics Investigation of the pH Regulation Mechanism of Dinoflagellate Luciferase

Abstract

The bioluminescence reaction in dinoflagellates involves the oxidation of an open-chain tetrapyrrole by the enzyme dinoflagellate luciferase (LCF). The activity of LCF is tightly regulated by pH, where the enzyme is essentially inactive at pH ∼8 and optimally active at pH ∼6. Little is known about the mechanism of LCF or the structure of the active form of the enzyme, although it has been proposed that several intramolecularly conserved histidine residues in the N-terminal region are important for the pH regulation mechanism. Here, constant pH accelerated molecular dynamics was employed to gain insight into the conformational activation of LCF induced by acidification.

A “weak acid and weak base” type fluorescent probe for sensing pH: mechanism and application in living cells

“…19,20 However, studies on both extremely acidic pH probes (pH < 4.00) and extremely basic pH probes (pH > 8.00) are rare and mostly single regions. 21,22 It is difficult for most organisms to survive under highly acidic or alkaline conditions, 23 but a large number of microorganisms, such as acidophilus and Helicobacter pylori, [24][25][26] prefer harsh environments. 27,28 Therefore, it is of great signicance for medical rehabilitation to detect the pH value of lesion location as soon as possible and accurately administer drugs to kill bacteria.…”

New Perspectives Related to the Bioluminescent System in Dinoflagellates: Pyrocystis lunula, a Case Study

“…For LCF, the activity is regulated by the protonation state of the histidine residues located outside the active site [72]. Recently, Donnan et al [73] applied Constant pH Molecular Dynamics to study the structural changes linked with the activation of LCF upon acidification. The protonation of some residues, including the previously reported intra-molecularly conserved histidines, and the H1064/H1065 dyad (inside the catalytic domain), correlates with a large-scale structural change in which the helical bundle domains are regrouped to allow luciferin access to the active site.…”