ASD v2.0: updated content and novel features focusing on allosteric regulation

Abstract

Allostery is the most direct and efficient way for regulation of biological macromolecule function and is induced by the binding of a ligand at an allosteric site topographically distinct from the orthosteric site. AlloSteric Database (ASD, http://mdl.shsmu.edu.cn/ASD) has been developed to provide comprehensive information on allostery. Owing to the inherent high receptor selectivity and lower target-based toxicity, allosteric regulation is expected to assume a more prominent role in drug discovery and bioengineering, leading to the rapid growth of allosteric findings. In this updated version, ASD v2.0 has expanded to 1286 allosteric proteins, 565 allosteric diseases and 22 008 allosteric modulators. A total of 907 allosteric site-modulator structural complexes and >200 structural pairs of orthosteric/allosteric sites in the allosteric proteins were constructed for researchers to develop allosteric site and pathway tools in response to community demands. Up-to-date allosteric pathways were manually curated in the updated version. In addition, both the front-end and the back-end of ASD have been redesigned and enhanced to allow more efficient access. Taken together, these updates are useful for facilitating the investigation of allosteric mechanisms, allosteric target identification and allosteric drug discovery.

Human 60-kDa Lysophospholipase Contains an N-terminal l-Asparaginase Domain That Is Allosterically Regulated by l-Asparagine

“…Based on the observed sigmoidal kinetic behavior and the monomeric state of hASNase1, it appears plausible to assume that this is another example of a monomeric enzyme exhibiting positive allosteric regulation. Importantly, given the fact that L-Asn plays a dual role of being both substrate and regulator of hASNase1, L-Asn can be considered as a homotropic allosteric effector of this enzyme, adding to the steadily growing number of allosterically regulated proteins (63).…”

Prediction of HBF-0259 interactions with hepatitis B Virus receptors and surface antigen secretory factors

“…The interaction energy of HBF-0259 to PreS1 and PreS2 [1][2][3][4][5][6][7][8][9][10][11] were lower comparing to other predicted receptors. HBF-0259 obviously interacts more strongly with SCCA1.…”

“…We also used Hex 8.0.0 in docking of HBF-0259 together with any of Alisporivir, NIM811, SCY635 and Sanglifehrin A compounds in correlation with secretory molecules. Since ASGPR/FNIII1 and SCCA1/ Pre-S1 [8,31] ASGPRCRD [41] and SCCA1 [8] 1DV8 [17] and 2ZV6 [43] Pre-S2 [3,8] FTL [8] and FNIII 1 [41] 2FG4 [35] and 2HA1 [34] Pre-S1 [20 [7,9].…”

“…Amino acids involved in interaction site of HBF-0259 were analyzed for conservancies among target molecules including, SCCA1, FNIII 1 , preS2 [1][2][3][4][5][6][7][8][9][10][11] , NTCP 84-165 , FTL, ASGPRCRD, preS1 . The results showed no conserved sequences in any of mentioned receptors ( Table 2).…”

“…In this study, in order to predict the mechanism(s) of action by which HBF-0259 decreases HBsAg secretion, we predict the interaction of HBF-0259 with suggested HBV receptors, preS regions of HBsAg (preS1 and preS2 [1][2][3][4][5][6][7][8][9][10][11] ) and cellular HBsAg secreting factors by computational approaches (Table 1).…”