Structure and backbone dynamics of vanadate-bound PRL-3: comparison of 15N nuclear magnetic resonance relaxation profiles of free and vanadate-bound PRL-3
| Autor: | Ki-Woong Jeong, Eun-Jung Lee, Areum Shin, Bonghwan Jin, Eunhee Kim, Eunice EunKyeong Kim, Young-Guen Park, Yangmee Kim, Dong-Il Kang, Chung-Kyoung Lee, Young Ho Jeon |
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| Rok vydání: | 2014 |
| Předmět: |
Magnetic Resonance Spectroscopy
biology Stereochemistry Chemistry Active site Protein tyrosine phosphatase Nuclear magnetic resonance spectroscopy Plasma protein binding Biochemistry Protein Structure Secondary Neoplasm Proteins Protein Structure Tertiary Nuclear magnetic resonance Protein structure Hydrolase Helix biology.protein Humans Vanadate Protein Tyrosine Phosphatases Vanadates hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Biochemistry. 53(29) |
| ISSN: | 1520-4995 |
| Popis: | 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 α4-α6, and the polybasic region. Compared to free PRL-3, vanadate-bound PRL-3 has a longer α4 helix, where the catalytic R110 residue coordinates with vanadate in the active site. In addition, the hydrophobic cavity formed by helices α4-α6 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. |
| Databáze: | OpenAIRE |
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