PinA from Aspergillus nidulans binds to pS/pT-P motifs using the same Loop I and XP groove as mammalian Pin1.
Binding of the Cdc25c-T48 ligand to PinA from Aspergillus nidulans has been characterised by the identification of 15N and 1H resonances from 1H-15N HSQC NMR titration experiments using previous backbone assignments. It is shown that the binding site for the Cdc25c-T48 ligand with PinA is the same as in the mammalian protein Pin1, although with a reduced binding affinity. It had previously been proposed that the arginine residue (R17) in the loop I region of the Pin1 WW domain is essential for binding to the pSer/pThr-Pro motifs of phosphorylated ligands such as Cdc25c. In PinA, a fungal homologue of Pin1, the arginine residue (R17) is replaced with an asparagine residue (N17). The effect of substitution of R17 by N17 in Pin1 has been investigated via a computational study, which predicted that changing R17 to N17 in Pin1 lowers the ligand binding affinity as a result of reduced hydrogen bonding between the protein and the phosphate group of the ligand.
Kato
Yusuke
Y
Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraqi 305-8566, Japan.
Ng
Chai Ann
CA
Brownlee
Robert T C
RT
Tanokura
Masaru
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001233:Aspergillus nidulans / Q000201:enzymology; D018797:Cell Cycle Proteins / Q000737:chemistry; D006801:Humans; D008024:Ligands; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019906:Nuclear Magnetic Resonance, Biomolecular; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D017433:Protein Structure, Secondary; D020349:Surface Plasmon Resonance; D020687:cdc25 Phosphatases / Q000737:chemistry
D018797:Cell Cycle Proteins; D008024:Ligands; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase