Paper Citing NAMD - Abstract
Olmez, Elif Ozkirimli; Alakent, Burak
Alpha7 Helix Plays an Important Role in the Conformational Stability of PTP1B
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 28:675-693, APR 2011
The C-terminus of Protein Tyrosine Phosphatase 1B (PTP1B) includes an alpha-helix (alpha 7), which forms an allosteric binding site 20 angstrom away from the active site. This helix is specific to PTP1B and its truncation decreases the catalytic activity significantly. Here, molecular dynamics (MD) simulations in the presence and absence of alpha 7 were performed to investigate the role played by alpha 7. The highly mobile alpha 7 was found to maintain its contacts with loop 11 (L11)-alpha 3 helix throughout the simulations. The interactions of Tyr152 on L11, Tyr176, Thr177 on the catalytically important WPD loop and Ser190 on alpha 3 are important for the conformational stability and the concerted motions of the regions surrounding the WPD loop. In the absence of alpha 7, L11 and WPD loop move away from their crystal structure conformations, resulting in the loss of the interactions in this region, and a decrease in the residue displacement correlations in the vicinity of WPD loop. Therefore, we suggest that one of the functionally important roles of alpha 7 may be to limit the L11 and alpha 3 motions, and, facilitate the WPD loop motions. Truncation of alpha 7 in PTP1B is found to affect distant regions as well, such as the substrate recognition site and the phosphate binding-loop (P-loop), changing the conformations of these regions significantly. Our results show that the PTP1B specific alpha 7 is important for the conformation and dynamics of the WPD loop, and also may play a role in ligand binding.
