A measure of the promiscuity of proteins and characteristics of residues in the vicinity of the catalytic site that regulate promiscuity.

PloS One
Sandeep Chakraborty, Basuthkar J Rao

Abstract

Promiscuity, the basis for the evolution of new functions through 'tinkering' of residues in the vicinity of the catalytic site, is yet to be quantitatively defined. We present a computational method Promiscuity Indices Estimator (PROMISE)--based on signatures derived from the spatial and electrostatic properties of the catalytic residues, to estimate the promiscuity (PromIndex) of proteins with known active site residues and 3D structure. PromIndex reflects the number of different active site signatures that have congruent matches in close proximity of its native catalytic site, the quality of the matches and difference in the enzymatic activity. Promiscuity in proteins is observed to follow a lognormal distribution (μ = 0.28, σ = 1.1 reduced chi-square = 3.0E-5). The PROMISE predicted promiscuous functions in any protein can serve as the starting point for directed evolution experiments. PROMISE ranks carboxypeptidase A and ribonuclease A amongst the more promiscuous proteins. We have also investigated the properties of the residues in the vicinity of the catalytic site that regulates its promiscuity. Linear regression establishes a weak correlation (R(2)∼0.1) between certain properties of the residues (charge, polar, etc) in...Continue Reading

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Citations

Oct 30, 2014·Biochemistry·Jessica K LukowskiR Jeremy Johnson
Sep 15, 2014·The Journal of Steroid Biochemistry and Molecular Biology·William M Atkins
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Apr 12, 2020·International Journal of Biological Macromolecules·C H VidyaSridevi Annapurna Singh

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Software Mentioned

iscuity I ndice s E stimator ( PROMISE )
CLASP
Prom
CSA
BioPerl
Emboss
PromIndex
Gnuplot
PDB2PQR
CPAN

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