Multiconformation continuum electrostatics analysis of the NhaA Na+/H+ antiporter of Escherichia coli with functional implications.

Content Provider	Semantic Scholar
Author	Olkhova, Elena Hunte, Carola Screpanti, Emanuela Padan, Etana Michel, Hartmut
Copyright Year	2006
Abstract	Sodium proton antiporters are essential enzymes that catalyze the exchange of sodium ions for protons across biological membranes. Protonations and deprotonations of individual amino acid residues and of clusters formed by these residues play an important role in activating these enzymes and in the mechanism of transport. We have used multiconformation continuum electrostatics method to investigate the protonation states of residues in the sodium proton exchanger NhaA from Escherichia coli, the structure of which has been determined recently by x-ray crystallography. Our calculations identify four clusters of electrostatically tightly interacting residues as well as long-range interactions between residues required for activation. The importance of many of these residues has been demonstrated by the characterization of site-directed mutants. A number of residues with extreme pKa values, including several of the "pH sensor," can only undergo protonation/deprotonation reactions subsequent to conformational changes. The results of the calculations provide valuable information on the activation of the antiporter and the role of individual amino acid residues, and provide a solid framework for further experiments.
Starting Page	144
Ending Page	149
Page Count	6
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.pnas.org/content/103/8/2629.full.pdf
PubMed reference number	16477015v1
Volume Number	103
Issue Number	8
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Subject Keyword	Amino Acids Crystallography Crystallography, X-Ray Ions Protons Sodium Cation antiporter mutant
Content Type	Text
Resource Type	Article