2MBC

Solution Structure of human holo-PRL-3 in complex with vanadate

Summary for 2MBC

• Entry DOI: 10.2210/pdb2mbc/pdb
• Related: 1R6H 1V3A
• NMR Information: BMRB: 19395
• Descriptor: Protein tyrosine phosphatase type IVA 3 (1 entity in total)
• Functional Keywords: holo-prl-3, vanadate, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane : O75365
• Total number of polymer chains: 1
• Total formula weight: 18268.29

Authors

Jeong, K.,Kang, D.,Kim, J.,Shin, S.,Jin, B.,Lee, C.,Kim, E.,Jeon, Y.H.,Kim, Y. (deposition date: 2013-07-29, release date: 2013-10-09, Last modification date: 2024-05-15)

Primary citation

Jeong, K.W.,Kang, D.I.,Lee, E.,Shin, A.,Jin, B.,Park, Y.G.,Lee, C.K.,Kim, E.H.,Jeon, Y.H.,Kim, E.E.,Kim, Y.
Structure and backbone dynamics of vanadate-bound PRL-3: comparison of 15N nuclear magnetic resonance relaxation profiles of free and vanadate-bound PRL-3.
Biochemistry, 53:4814-4825, 2014

PubMed 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 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 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 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.

PubMed: 24983822
DOI: 10.1021/bi5003844

Experimental method

SOLUTION NMR