title: Predicting functional residues of the Solanum lycopersicum aspartic protease inhibitor (SLAPI) by combining sequence and structural analysis with molecular docking.
abstract: The Solanum lycopersicum aspartic protease inhibitor (SLAPI), which belongs to the STI-Kunitz family, is an effective inhibitor of the aspartic proteases human cathepsin D and Saccharomyces proteinase A. However, in contrast with the large number of studies on the inhibition mechanism of the serine proteases by the STI-Kunitz inhibitors, the structural aspects of the inhibition mechanism of aspartic proteases from this family of inhibitors are poorly understood. In the present study, we have combined sequence and structural analysis methods with protein-protein docking to gain a better understanding of the SLAPI inhibition mechanism of the proteinase A. The results suggest that: i) SLAPI loop L9 may be involved in the inhibitor interaction with the proteinase A´s active site, and ii) the residues I144, V148, L149, P151, F152 and R154 are implicated in the difference in the potency shown previously by SLAPI and another STI-Kunitz inhibitor isolated from Solanum tuberosum to inhibit proteinase A. These results will be useful in the design of site directed mutagenesis experiments to understand more thoroughly the aspartic protease inhibition mechanism of SLAPI and other related STI-Kunitz inhibitors.
authors.affiliation: Centro de Estudio de Proteínas (CEP), Facultad de Biología, Universidad de La Habana, Vedado, La Habana, Cuba. yaselg@gmail.com
authors.forename: Yasel
authors.initials: Y
authors.lastname: Guerra
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Valiente
authors.forename: Colin
authors.initials: C
authors.lastname: Berry
authors.forename: Tirso
authors.initials: T
authors.lastname: Pons
mesh_terms: D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D020134:Catalytic Domain; D003198:Computer Simulation; D017124:Conserved Sequence; D018551:Solanum lycopersicum; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D020539:Sequence Analysis, Protein; D013499:Surface Properties
chemical_list: D010940:Plant Proteins; D029701:Saccharomyces cerevisiae Proteins; D016282:Aspartic Acid Endopeptidases; C022442:aspergillopepsin II
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