Physicochemical characterization of an aspin (rBm-33) from a filarial parasite Brugia malayi against the important human aspartic proteases

Nagampalli Raghavendra Sashi Krishna, N. S.A. Krushna, R. B. Narayanan, S. S. Rajan, K. Gunasekaran

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2 Citations (Scopus)

Abstract

The aspartic protease inhibitory efficiency of rBm-33, an aspin from a filarial parasite Brugia malayi was investigated. rBm-33 was found to be thermostable up to 90°C and it forms a stable 'enzyme-product' complex with human pepsin. Aspartic protease inhibitory activity was investigated using UV spectroscopy and isothermal titration calorimetry. Our results suggest that rBm-33 inhibits the activity of important human aspartic proteases that were examined with binding constants (Kb) values between 10.23 × 103 and 6.52 × 103 M-1. The binding reactions were enthalpy driven with ΔHb values between -50.99 and -46.07 kJ mol -1. From kinetic studies, pepsin inhibition by rBm-33 was found to be linear competitive with an inhibition constant (Ki) of 2.5 (±0.8) nM. Because of the inhibitory efficacy of Bm-33 against important human aspartic proteases which play a vital role in immune-regulation along with other functions, Bm-33 can be projected as a drug target for the filariasis.

Original languageEnglish
Pages (from-to)1054-1060
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume28
Issue number5
DOIs
Publication statusPublished - 1 Oct 2013
Externally publishedYes

Keywords

  • Aspartic proteases
  • Brugia malayi
  • Competitive inhibition
  • Drug target
  • Filariasis
  • Thermal stability

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