Molecular determinant for specificity: Differential interaction of α-amylases with their proteinaceous inhibitors

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 12; p. 129703
• Main Authors: Rane, Ashwini S., Joshi, Rakesh S., Giri, Ashok P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2020
• Subjects: Active site; active sites; alpha-amylase; alpha-Amylases - chemistry; alpha-Amylases - metabolism; Amino Acid Sequence; Animals; chlorides; disulfides; Evolution, Molecular; glutamine; Herbivory; Humans; Insect; Insecta - chemistry; Insecta - enzymology; Insecta - metabolism; insects; mammals; Models, Molecular; Molecular interactions; Plants - chemistry; Plants - enzymology; Plants - metabolism; Protein Conformation; Proteolysis; Sequence Alignment; Substrate Specificity; α-Amylase; α-Amylase inhibitor; α-Amylase; Insect; α-Amylase inhibitor; Molecular interactions; Active site
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2020.129703

α-Amylase inhibitors (α-AIs) belong to the discrete classes, and exhibited differential specificities against α-amylases from various sources. Several α-amylases and their complexes with inhibitors at the molecular level have been studied in detail. Interestingly, some α-AIs depict specific and selective interactions amid different insect α-amylases. There are studies to understand evolutionary variability and functional differentiation of insect α-amylases and their cognate inhibitors. We have examined sequence, structural, and interaction diversity between various α-amylases and α-AIs. Based on these analyses, we are providing a potential basis for the functional differentiation among certain insect α-amylases concerning mammalian counterparts and their interactions with different proteinaceous α-AIs. Insect α-amylases have conserved domain architecture with differences in length, number of disulfide bonds, and secondary structure. Furthermore, few of them exhibit variable characteristics like chloride dependent activity, the presence of N-terminal glutamine residue to protect against proteolytic degradation, and loop variations near the enzyme active site. Conformation of α-AI protein could be an essential factor for their specificity and binding affinities towards target α-amylase(s). Furthermore, variation into the enzyme binding pocket residues might contribute to differential interactions with inhibitors. Molecular insights in the interactions between insect α-amylases and plant α-AI will provide the details of mechanisms assisting the inhibitor specificity. Furthermore, this information will help to design potent and effective α-AIs against specific α-amylase. [Display omitted] •Food source is the key factor for expression dynamics of the insect amylases.•Binding pocket variability contributes to the amylases substrate specificities.•Loop variability determines the inhibitor specificity of α-amylases.•Specificity and binding affinities could be affected by conformation of α-AI.