ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Brownian dynamics simulations of the interactions between lactate dehydrogenase (LDH) and G- or F-actin. Part II: mixed isoforms

Eric N. Njabon, Neville Y. Forlemu, Alphonse Emadak, Victor F. Waingeh, and Kathryn A. Thomasson

Faculty of Science, Laboratory of Physical and Theoretical Chemistry, University of Yaoundé, Yaoundé I, Cameroon

E-mail: eric.njankwa@facsciences-uy1.cm

Received: 4 August 2020  Accepted: 8 December 2020

Abstract:

Experimental studies have shown that many glycolytic enzymes bind cytoskeletal proteins reversibly including lactate dehydrogenase (LDH) and that the interaction may be electrostatic in nature. LDH is particularly interesting because different isoforms have different binding affinities. Herein, Brownian dynamics simulations examine the interactions of mixed LDH isoforms with F-actin based on models of human muscle (M) and heart (H) isoforms and rabbit muscle (M) and heart (H) isoforms built via homology modeling from a variety of mammalian forms of the enzyme. The LDH-mixed tetrameric isoforms, LDH-M₃H, LDH-M₂H₂, LDH-MH₃, give distinctive electrostatic potentials and charges; + 6.9 e for human LDH-M₃H, −9.4 e for human LDH-MH₃, the LDH-M₂H₂ gives three distinctively different pictures of the electrostatic potential and show different binding affinity depending on the nature of the quaternary structure of the tetramer. If the positive charge patch of LDH-M₄ between subunits A/D and subunits B/C, which was identified as the binding site of LDH to F-actin for the muscle isoform (Part I of the companion paper), remains intact on one side of LDH-M₂H₂, the mixed isoform can still bind F-actin. If, however, the LDH-M₂H₂ isoform does not maintain this positively charged patch, the mixed isoform does not bind as strongly.

Keywords: Brownian dynamics; Free energy; Protein–protein interactions; Glycolytic enzymes; Electrostatic interactions; LDH-mixed isoforms

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-020-01463-0

Chemical Papers 75 (5) 1937–1948 (2021)