2mbc

Publication Abstract from PubMed

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 the P-loop of protein tyrosine phosphatases is closely related to their catalytic activity. Using nuclear magnetic resonance 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 in the WPD loop, P-loop, helices alpha4-alpha6, and the polybasic region. Compared to free PRL-3, vanadate-bound PRL-3 has a longer alpha4 helix, where the catalytic R110 residue coordinates with vanadate in the active site. In addition, the hydrophobic cavity formed by helices alpha4-alpha6 with a depth of 14-15 A 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 k(close) of 7 s(-1). This intrinsic loop flexibility of PRL-3 may be related to their catalytic rate and may play a role in substrate recognition.

Structure and backbone dynamics of vanadate-bound PRL-3: comparison of 15N nuclear magnetic resonance relaxation profiles of free and vanadate-bound PRL-3.,Jeong KW, Kang DI, Lee E, Shin A, Jin B, Park YG, Lee CK, Kim EH, Jeon YH, Kim EE, Kim Y Biochemistry. 2014 Jul 29;53(29):4814-25. doi: 10.1021/bi5003844. Epub 2014 Jul, 14. PMID:24983822^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.