Structure and Backbone Dynamics of vanadate-bound PRL-3: Comparison of 15N NMR Relaxation Profiles of free and vanadate-bound PRL-3.
Related Articles Structure and Backbone Dynamics of vanadate-bound PRL-3: Comparison of 15N NMR Relaxation Profiles of free and vanadate-bound PRL-3.
Biochemistry. 2014 Jul 1;
Authors: Jeong KW, Kang DI, Lee E, Shin A, Jin B, Park YG, Lee CK, Kim EH, Jeon YH, Kim EE, Kim Y
Abstract
Phosphatases of regenerating liver (PRLs) constitute a novel class of small, prenylated phosphatases with oncogenic activity. PRL-3 is particularly important in cancer metastasis and represents a potential, therapeutic target. The flexibility of the WPD loop as well as P-loop of protein tyrosine phosphatases is closely related to their catalytic activity. Using nuclear magnetic resonance (NMR) spectroscopy, we studied the structure of vanadate-bound PRL-3, which was generated by addition of sodium orthovanadate to PRL-3. The WPD loop of free PRL-3 extended outside of the active site, forming an open conformation, whereas that of vanadate-bound PRL-3 was directed into the active site by a large movement, resulting in a closed conformation. We suggest that vanadate binding induced structural changes of the WPD loop, P-loop, ?4-?6 helices, and polybasic region. Compared to free PRL-3, vanadate-bound PRL-3 has a longer ?4 helix, where the catalytic R110 residue coordinates with vanadate in the active site. In addition, the hydrophobic cavity formed by ?4-?6 helices with a depth of 14-15 Å can accommodate a farnesyl chain at the truncated prenylation motif of PRL-3, i.e., from R169 to M173. Conformational exchange data suggested that the WPD loop moves between open and closed conformations with a closing rate constant kclose of 7 s-1. This intrinsic loop flexibility of PRL-3 may be related to their catalytic rate and may play a role in the substrate recognition.
PMID: 24983822 [PubMed - as supplied by publisher]
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