Structure of human PRL-3, the phosphatase associated with cancer metastasis.
PRL-3, a novel class protein of prenylated tyrosine phosphatase, is important in cancer metastasis. Due to its high levels of expression in metastatic tumors, PRL-3 may constitute a useful marker for metastasis and might be a new therapeutic target. Here, we present the solution structure of the phosphatase domain of a human PRL-3 (residues 1-162) in phosphate-free state. The nuclear magnetic resonance (NMR) structure of PRL-3 is similar to that of other known phosphatases with minor differences in the secondary structure. But the conformation and flexibility of the loops comprising the active site differ significantly. When phosphate ions or sodium orthovanadate, which is a known inhibitor, are added to the apo PRL-3, the NMR signals from the residues in the active site appeared and could be assigned, indicating that the conformation of the residues has been stabilized.
Kim
Kyoung-Ah
KA
Magnetic Resonance Team, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
Song
Jin-Sue
JS
Jee
JunGoo
J
Sheen
Mee Rie
MR
Lee
Chulhyun
C
Lee
Tae Gyu
TG
Ro
Seonggu
S
Cho
Joong Myung
JM
Lee
Weontae
W
Yamazaki
Toshio
T
Jeon
Young Ho
YH
Cheong
Chaejoon
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry*; D007477:Ions; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010710:Phosphates / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014443:Tyrosine / Q000737:chemistry; D014638:Vanadates / Q000737:chemistry / Q000494:pharmacology
D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D007477:Ions; D008024:Ligands; D009363:Neoplasm Proteins; D010710:Phosphates; D014638:Vanadates; D014443:Tyrosine; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases