A similar feature has been reported in other proteins that help to form stable dimers Structure of Mtb ICL.
(A) Ribbon structure of the homotetrameric Mtb ICL, with each subunit shown in different color (PDB ID: 1F8I). Alterations in amino acid sequence could affect the native 3D conformation of the protein structure and to estimate the conformational modifications, MD simulations can be used for an in-depth analysis.
An unusual α/β barrel consisting of eight α-helices (α4–α11) and eight β-strands (β2-β5, β8, β12–β14) forms the larger domain of the enzyme.
This data can be used to study global, correlated motions in atomic simulations of proteins.
Isocitrate lyase (ICL), one of the key enzymes of glyoxylate shunt, catalyzes the transformation of isocitrate to succinate and glyoxylate.
It reveals internal dynamics of the enzyme structure and also suggests that regions other than the active site should be exploited for targeting Mtb ICL inhibition and development of novel anti-tuberculosis compounds..
Thus, the structural dynamics and flexibility play an important role in the function of proteins.
(B) Chain A of Mtb ICL tetramer showing the position of Phe345 in red and active site signature sequence () in green. The active site residues and Phe345 are marked and labeled. There are few reports that show the activity of an enzyme can be lost by a mutation topologically distant from active site.