Jeong, Ki-Woong Kang, Dong-Il Lee, Eunjung Shin, Areum Jin, Bonghwan Park, Young-Guen Lee, Chung-Kyoung Kim, Eun-Hee Jeon, Young Ho Kim, Eunice Eunkyeong Kim, Yangmee 2024-01-20T09:30:42Z 2024-01-20T09:30:42Z 2021-09-05 2014-07-29 0006-2960 https://pubs.kist.re.kr/handle/201004/126574 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 alpha 4-alpha 6, and the polybasic region. Compared to free PRL-3, vanadate-bound PRL-3 has a longer alpha 4 helix, where the catalytic R110 residue coordinates with vanadate in the active site. In addition, the hydrophobic cavity formed by helices alpha 4-alpha 6 with a depth of 14-15 angstrom 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. English AMER CHEMICAL SOC PROTEIN-TYROSINE PHOSPHATASES HEPARIN-BINDING DOMAIN MODEL-FREE APPROACH NMR RELAXATION REGENERATING LIVER CELL-GROWTH IDENTIFICATION METASTASIS EXPRESSION MECHANISM Structure and Backbone Dynamics of Vanadate-Bound PRL-3: Comparison of N-15 Nuclear Magnetic Resonance Relaxation Profiles of Free and Vanadate-Bound PRL-3 Article 10.1021/bi5003844 1 BIOCHEMISTRY, v.53, no.29, pp.4814 - 4825 BIOCHEMISTRY 53 29 4814 4825 scie scopus 000339686600008 2-s2.0-84905020120 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article PROTEIN-TYROSINE PHOSPHATASES HEPARIN-BINDING DOMAIN MODEL-FREE APPROACH NMR RELAXATION REGENERATING LIVER CELL-GROWTH IDENTIFICATION METASTASIS EXPRESSION MECHANISM