Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Nov 26, 2015; 6(4): 366-378
Published online Nov 26, 2015. doi: 10.4331/wjbc.v6.i4.366
Disruption of NAD+ binding site in glyceraldehyde 3-phosphate dehydrogenase affects its intranuclear interactions
Manali Phadke, Natalia Krynetskaia, Anurag Mishra, Carlos Barrero, Salim Merali, Scott A Gothe, Evgeny Krynetskiy
Manali Phadke, Natalia Krynetskaia, Carlos Barrero, Salim Merali, Scott A Gothe, Evgeny Krynetskiy, Temple University School of Pharmacy, Philadelphia, PA 19140, United States
Natalia Krynetskaia, Anurag Mishra, Evgeny Krynetskiy, Jayne Haines Center for Pharmacogenomics and Drug Safety, Temple University, Philadelphia, PA 19140, United States
Author contributions: Krynetskaia N and Krynetskiy E designed the research, analyzed and evaluated data; Phadke M, Mishra A and Barrero C performed the experiments and prepared corresponding sections for the manuscript; Merali S analyzed MS data; Gothe SA performed molecular modeling and data evaluation; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published.
Supported by The National Cancer Institute, No. R01-CA104729; Jayne Haines Center for Pharmacogenomics and Drug Safety of Temple University School of Pharmacy and Temple University Summer Research Award (to Evgeny Krynetskiy).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Evgeny Krynetskiy, PhD, DSc, Associate Professor, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, United States. ekrynets@temple.edu
Telephone: +1-215-7074257 Fax: +1-215-7073678
Received: April 29, 2015
Peer-review started: April 30, 2015
First decision: August 20, 2015
Revised: September 1, 2015
Accepted: September 29, 2015
Article in press: September 30, 2015
Published online: November 26, 2015
Processing time: 208 Days and 8.2 Hours
Core Tip

Core tip: We detected the phosphorylated amino acid residues Y94, S98, T99 within the NAD+ binding center of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Substitution of these amino acids with non-phosphorylated alanine residues did not abrogate intranuclear localization of GAPDH. Instead, such mutations altered the molecular dynamics parameters of intranuclear GAPDH probably by hindering its interactions with yet to be identified nuclear biomolecules. Our molecular modeling experiments invoke an important structural feature -T99-E97 H-bond likely involved in stabilization of NAD+ binding center.