Insight into Structure-Function Relationships of β-Lactamase and BLIPs Interface Plasticity using Protein-Protein Interactions

Tara C Yadav; Vidhu Agarwal; Amit K Srivastava; Navdeep Raghuwanshi; Pritish Varadwaj; Ramasare Prasad; Vikas Pruthi

doi:10.2174/1381612825666190911154650

Insight into Structure-Function Relationships of β-Lactamase and BLIPs Interface Plasticity using Protein-Protein Interactions

Curr Pharm Des. 2019;25(31):3378-3389. doi: 10.2174/1381612825666190911154650.

Authors

Tara C Yadav¹, Vidhu Agarwal², Amit K Srivastava¹, Navdeep Raghuwanshi³, Pritish Varadwaj², Ramasare Prasad¹, Vikas Pruthi¹

Affiliations

¹ Department of Biotechnology, Indian Institute of Technology, Roorkee-247667, Uttarakhand, India.
² Department of Bioinformatics, Indian Institute of Information Technology, Allahabad 211015, India.
³ Vaccine Formulation & Research Center, Gennova (Emcure) Biopharmaceuticals Limited, Pune - 11057, Maharashtra, India.

PMID: 31544712
DOI: 10.2174/1381612825666190911154650

Abstract

Background: Mostly BLIPs are identified in soil bacteria Streptomyces and originally isolated from Streptomyces clavuligerus and can be utilized as a model system for biophysical, structural, mutagenic and computational studies. BLIP possess homology with two proteins viz., BLIP-I (Streptomyces exofoliatus) and BLP (beta-lactamase inhibitory protein like protein from S. clavuligerus). BLIP consists of 165 amino acid, possessing two homologues domains comprising helix-loop-helix motif packed against four stranded beta-sheet resulting into solvent exposed concave surface with extended four stranded beta-sheet. BLIP-I is a 157 amino acid long protein obtained from S. exofoliatus having 37% sequence identity to BLIP and inhibits beta-lactamase.

Methods: This review is intended to briefly illustrate the beta-lactamase inhibitory activity of BLIP via proteinprotein interaction and aims to open up a new avenue to combat antimicrobial resistance using peptide based inhibition.

Results: D49A mutation in BLIP-I results in a decrease in affinity for TEM-1 from 0.5 nM to 10 nM (Ki). It is capable of inhibiting TEM-1 and bactopenemase and differs from BLIP only in modulating cell wall synthesis enzyme. Whereas, BLP is a 154 amino acid long protein isolated from S. clavuligerus via DNA sequencing analysis of Cephamycin-Clavulanate gene bunch. It shares 32% sequence similarity with BLIP and 42% with BLIP-I. Its biological function is unclear and lacks beta-lactamase inhibitory activity.

Conclusion: Protein-protein interactions mediate a significant role in regulation and modulation of cellular developments and processes. Specific biological markers and geometric characteristics are manifested by active site binding clefts of protein surfaces which determines the specificity and affinity for their targets. TEM1.BLIP is a classical model to study protein-protein interaction. β-Lactamase inhibitory proteins (BLIPs) interacts and inhibits various β-lactamases with extensive range of affinities.

Keywords: Streptomyces exofoliatus; antimicrobial resistance; protein-protein interactions; β-lactamase; β-lactamase inhibitory protein; β-lactams..

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Bacterial Proteins / chemistry*
Protein Interaction Mapping*
Streptomyces / chemistry*
Structure-Activity Relationship
beta-Lactamase Inhibitors / chemistry*
beta-Lactamases / chemistry*

Substances

Bacterial Proteins
beta-Lactamase Inhibitors
beta-Lactamases