Record Details

Prediction of inter domain interactions in modular polyketide synthases by docking and correlated mutation analysis

NIPGR Digital Knowledge Repository (NDKR)

View Archive Info
 
 
Field Value
 
Title Prediction of inter domain interactions in modular polyketide synthases by docking and correlated mutation analysis
 
Creator Yadav, Gitanjali
Anand, Swadha
Mohanty, Debasisa
 
Subject polyketide synthases
inter-domain interactions
evolutionary analysis
protein-protein docking
correlated mutations
interface prediction
 
Description Accepted date: 3 Jan 2012
Polyketide synthases (PKSs) are huge multi-enzymatic protein complexes involved in the biosynthesis of one of the largest families of bioactive natural products, namely polyketides. The specificity of interactions between various catalytic domains of these megasynthases is one of the pivotal factors which control the precise order in which the extender units are joined during the biosynthetic process. Hence, understanding the molecular details of protein-protein interactions in the PKS megasynthases would be crucial for rational design of novel polyketides by domain swapping experiments involving engineered combinations of PKS catalytic domains. We have developed a computational method for exploring the binding interface between two proteins, and used it to identify the interacting residue pairs, which govern the specificity of recognition between acyl carrier protein (ACP) domain and two core catalytic domains, namely the ketosynthase (KS) and acyl transferase (AT). Both of these domain interactions i.e. the KS-ACP and the AT-ACP, are likely to play a major role in channelling of substrates and control of specificity during polyketide biosynthesis. The method, called interface scan, uses a combination of geometric docking and evolutionary information for the identification of the most appropriate mode of association between two proteins. The parameters of interface scan have been standardized based on analysis of contacts in the crystal structure of ACP in complex with ACP synthase (AcpS). Many of the contacts predicted for PKS domains are in agreement with available experiments.
Authors thank Director, NII for encouragement and support.
G.Y. and S.A. were recipients of Senior Research Fellowship
from CSIR, India. The work has been supported by grants to
National Institute of Immunology from Department of
Biotechnology, Government of India and grants to DM under
BTIS project of DBT, India.
 
Date 2015-11-26T07:07:55Z
2015-11-26T07:07:55Z
2013
 
Type Article
 
Identifier J. Biomol. Struct. Dyn., 31(1): 17-29.
http://172.16.0.77:8080/jspui/handle/123456789/386
http://www.tandfonline.com/doi/full/10.1080/07391102.2012.691342
10.1080/07391102.2012.691342
 
Language en_US
 
Publisher Taylor & Francis Group