Investigating Molecular Relationships Among Clinically Prevalent Aminoglycoside Phosphotransferases

7 Pages Posted: 11 Jun 2018

See all articles by K. Madhavi

K. Madhavi

Sri Padmavati Mahila Visvavidyalayam (SPMVV) - Department of Applied Microbiology

Lakshmi Jayasri Akkiraju

Sri Padmavati Mahila Visvavidyalayam (SPMVV) - Department of Applied Microbiology

V.V. Lakshmi

Sri Padmavati Mahila Visvavidyalayam (SPMVV) - Department of Applied Microbiology

Date Written: February 7, 2018

Abstract

Aminoglycosides constitute one of the most important class of antibiotics which are imperiled by the emergence of resistant organisms. Resistance to aminoglycosides is primarily due to enzymatic inactivation by several classes of aminoglycoside modifying enzymes including acetyl-transferases, nucleotidyl-transferases, and phospho-transferases. Among these Aminoglycoside phosphotransferases or kinases are an important class of antibiotic modifying enzymes which have been studied extensively. They are classified into seven different classes which include APH(2″)-I through IV, APH(3′)-I through VII, APH(3″)-I, APH(4)-I, APH(6)-I, APH(7″)-I APH(9)-I. Among these APH (2″) and APH (3′) groups are the largest and most prevalent clinically important enzymes. Several crystal structures of a number of APHs with diverse regiospecificity and substrate specificity have been elucidated.

The present study investigates the molecular changes which facilitated the adaptation and mutational evolution of clinically prevalent APHs and the phylogenetic relationship using bioinformatics tools. Multiple sequence alignment of these enzymes using ClustalW reveals the diversity among the most conserved residues and mutational changes which are crucial for inactivation of the aminoglycoside. The mutational profile of the most critically conserved residues obtained can play a key role in understanding the molecular details of resistance mediated by most clinically prevalent APHs.

Keywords: Aminoglycoside, APHs, ClustalW, Mutational profile

Suggested Citation

Madhavi, K. and Akkiraju, Lakshmi Jayasri and Lakshmi, V.V., Investigating Molecular Relationships Among Clinically Prevalent Aminoglycoside Phosphotransferases (February 7, 2018). 2018 IADS International Conference on Computing, Communications & Data Engineering (CCODE). Available at SSRN: https://ssrn.com/abstract=3183668 or http://dx.doi.org/10.2139/ssrn.3183668

K. Madhavi (Contact Author)

Sri Padmavati Mahila Visvavidyalayam (SPMVV) - Department of Applied Microbiology ( email )

Padmavathi Nagar, Near West Railway Station,
Andhra Pradesh
Tirupati, Andhra Pradesh 517502
India

Lakshmi Jayasri Akkiraju

Sri Padmavati Mahila Visvavidyalayam (SPMVV) - Department of Applied Microbiology

Padmavathi Nagar, Near West Railway Station,
Andhra Pradesh
Tirupati, Andhra Pradesh 517502
India

V.V. Lakshmi

Sri Padmavati Mahila Visvavidyalayam (SPMVV) - Department of Applied Microbiology ( email )

Padmavathi Nagar, Near West Railway Station,
Andhra Pradesh
Tirupati, Andhra Pradesh 517502
India

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