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

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.

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Faculty Opinions recommendation of Protein-protein interactions monitored in mammalian cells via complementation of beta -lactamase enzyme fragments.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1005525.65954 ◽

2002 ◽

Author(s):

Marilyn Parsons

Keyword(s):

Protein Interactions ◽

Mammalian Cells ◽

Beta Lactamase ◽

Protein Protein Interactions

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Theoretical models of inhibitory activity for inhibitors of protein–protein interactions: targeting menin–mixed lineage leukemia with small molecules

MedChemComm ◽

10.1039/c7md00170c ◽

2017 ◽

Vol 8 (12) ◽

pp. 2216-2227 ◽

Cited By ~ 4

Author(s):

Wiktoria Jedwabny ◽

Szymon Kłossowski ◽

Trupta Purohit ◽

Tomasz Cierpicki ◽

Jolanta Grembecka ◽

...

Keyword(s):

Small Molecules ◽

Binding Affinity ◽

Protein Interactions ◽

Empirical Model ◽

Inhibitory Activity ◽

Theoretical Models ◽

Mixed Lineage Leukemia ◽

Protein Protein Interactions ◽

Model Based ◽

Dispersion Terms

A computationally affordable, non-empirical model based on electrostatic multipole and dispersion terms successfully predicts the binding affinity of inhibitors of menin–MLL protein–protein interactions.

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Engineering an acetyllysine reader with photocrosslinking amino acid for interactome profiling

Chemical Communications ◽

10.1039/d1cc04611j ◽

2021 ◽

Author(s):

Babu Sudhamalla ◽

Anirban Roy ◽

Soumen Barman ◽

Jyotirmayee Padhan

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Protein Interactions ◽

Unnatural Amino Acids ◽

Protein Protein Interactions ◽

Site Specific ◽

Powerful Approach

The site-specific installation of light-activable crosslinker unnatural amino acids offers a powerful approach to trap transient protein-protein interactions both in vitro and in vivo. Herein, we engineer a bromodomain to...

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Engineering bromodomains with a photoactive amino acid by engaging ‘Privileged’ tRNA synthetases

Chemical Communications ◽

10.1039/c9cc09891g ◽

2020 ◽

Vol 56 (25) ◽

pp. 3641-3644

Author(s):

Shana Wagner ◽

Babu Sudhamalla ◽

Philip Mannes ◽

Sushma Sappa ◽

Sam Kavoosi ◽

...

Keyword(s):

Amino Acid ◽

Chemical Synthesis ◽

Protein Interactions ◽

Protein Protein Interactions ◽

Site Specific ◽

Trna Synthetases

An improved chemical synthesis, site-specific incorporation and enhanced photo-crosslinking ability of tmdF have been demonstrated in the context of protein–protein interactions.

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Identifying Antioxidant Proteins by Using Amino Acid Composition and Protein-Protein Interactions

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.591487 ◽

2020 ◽

Vol 8 ◽

Author(s):

Yixiao Zhai ◽

Yu Chen ◽

Zhixia Teng ◽

Yuming Zhao

Keyword(s):

Amino Acid ◽

Amino Acid Composition ◽

Acid Composition ◽

Protein Interactions ◽

Protein Protein Interactions ◽

Antioxidant Proteins

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Single Amino Acid Replacements in RocA Disrupt Protein-Protein Interactions To Alter the Molecular Pathogenesis of Group A Streptococcus

Infection and Immunity ◽

10.1128/iai.00386-20 ◽

2020 ◽

Vol 88 (11) ◽

Author(s):

Paul E. Bernard ◽

Amey Duarte ◽

Mikhail Bogdanov ◽

James M. Musser ◽

Randall J. Olsen

Keyword(s):

Amino Acid ◽

Protein Interactions ◽

Molecular Pathogenesis ◽

Single Amino Acid ◽

Accessory Protein ◽

Protein Protein Interactions ◽

Tissue Destruction ◽

Intact Cells ◽

Group A

ABSTRACT Group A Streptococcus (GAS) is a human-specific pathogen and major cause of disease worldwide. The molecular pathogenesis of GAS, like many pathogens, is dependent on the coordinated expression of genes encoding different virulence factors. The control of virulence regulator/sensor (CovRS) two-component system is a major virulence regulator of GAS that has been extensively studied. More recent investigations have also involved regulator of Cov (RocA), a regulatory accessory protein to CovRS. RocA interacts, in some manner, with CovRS; however, the precise molecular mechanism is unknown. Here, we demonstrate that RocA is a membrane protein containing seven transmembrane helices with an extracytoplasmically located N terminus and cytoplasmically located C terminus. For the first time, we demonstrate that RocA directly interacts with itself (RocA) and CovS, but not CovR, in intact cells. Single amino acid replacements along the entire length of RocA disrupt RocA-RocA and RocA-CovS interactions to significantly alter the GAS virulence phenotype as defined by secreted virulence factor activity in vitro and tissue destruction and mortality in vivo. In summary, we show that single amino acid replacements in a regulatory accessory protein can affect protein-protein interactions to significantly alter the virulence of a major human pathogen.

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Regulative interactions of the osmosensing C-terminal domain in the trimeric glycine betaine transporter BetP from Corynebacterium glutamicum

Biological Chemistry ◽

10.1515/bc.2009.068 ◽

2009 ◽

Vol 390 (8) ◽

Cited By ~ 10

Author(s):

Reinhard Krämer ◽

Christine Ziegler

Keyword(s):

Amino Acid ◽

Corynebacterium Glutamicum ◽

Protein Interactions ◽

Regulation Mechanism ◽

Protein Protein Interactions ◽

Molecular Switching ◽

X Ray ◽

X Ray Crystallography ◽

Terminal Domain ◽

Domain Reorientation

Abstract Activation of the osmoregulated trimeric betaine transporter BetP from Corynebacterium glutamicum was shown to depend mainly on the correct folding and integrity of its 55 amino acid long, partly α-helical C-terminal domain. Reorientation of the three C-terminal domains in the BetP trimer indicates different lipid-protein and protein-protein interactions of the C-terminal domain during osmoregulation. A regulation mechanism is suggested where this domain switches the transporter from the inactive to the active state. Interpretation of recently obtained electron and X-ray crystallography data of BetP led to a structure-function based model of C-terminal molecular switching involved in osmoregulation.

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