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PDBsum entry 2mbc
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References listed in PDB file
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Key reference
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Title
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Structure and backbone dynamics of vanadate-Bound prl-3: comparison of 15n nuclear magnetic resonance relaxation profiles of free and vanadate-Bound prl-3.
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Authors
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K.W.Jeong,
D.I.Kang,
E.Lee,
A.Shin,
B.Jin,
Y.G.Park,
C.K.Lee,
E.H.Kim,
Y.H.Jeon,
E.E.Kim,
Y.Kim.
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Ref.
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Biochemistry, 2014,
53,
4814-4825.
[DOI no: ]
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PubMed id
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Abstract
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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.
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