PDBsum entry 1pin

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Isomerase PDB id
Protein chain
153 a.a. *
1PG ×2
Waters ×204
* Residue conservation analysis

References listed in PDB file
Key reference
Title Structural and functional analysis of the mitotic rotamase pin1 suggests substrate recognition is phosphorylation dependent.
Authors R.Ranganathan, K.P.Lu, T.Hunter, J.P.Noel.
Ref. Cell, 1997, 89, 875-886. [DOI no: 10.1016/S0092-8674(00)80273-1]
PubMed id 9200606
The human rotamase or peptidyl-prolyl cis-trans isomerase Pin1 is a conserved mitotic regulator essential for the G2/M transition of the eukaryotic cell cycle. We report the 1.35 A crystal structure of Pin1 complexed with an AlaPro dipeptide and the initial characterization of Pin1's functional properties. The crystallographic structure as well as pH titration studies and mutagenesis of an active site cysteine suggest a catalytic mechanism that includes general acid-base and covalent catalysis during peptide bond isomerization. Pin1 displays a preference for an acidic residue N-terminal to the isomerized proline bond due to interaction of this acidic side chain with a basic cluster. This raises the possibility of phosphorylation-mediated control of Pin1-substrate interactions in cell cycle regulation.
Figure 1.
Figure 1. Overall Fold of Human Pin1(A) Ribbon representation of Pin1. Residues 1–6 and 40–44 are not visible in electron density maps and are disordered. Apostrophes distinguish the WW domain secondary structural elements from the PPIase domain's secondary structural features. Atoms are color coded for clarity (oxygen is red, nitrogen is blue, carbon is black, and sulfur is yellow). The HPO[4]^2− label reflects the possible substitution of sulfate by phosphate in phosphate-soaked crystals. Produced with MOLSCRIPT ([25]) and Raster3D ( [2]).(B) Ribbon and molecular surface representation of the Pin1 interdomain cavity. View is the same as in (A). The WW domain is orange and the PPIase domain is light blue. The dotted surface depicts the solvent-accessible surface for residues lining the interdomain cavity. The cavity presents a largely hydrophobic composite surface as indicated by the predominance of carbon atoms lining the cavity. Produced with RIBBONS ([5]).
Figure 3.
Figure 3. Structural Comparison of Representative PPIases(A) Cα stereo pair of FKBP (PDB code 1FKF), Pin1, and cyclophilin (PDB code 1CYH) aligned and offset. The backbone atoms of Pin1 and FKBP were aligned in O ([22]). Pin1 and cyclophilin (CyPA) were aligned by superimposing the backbone atoms of the cis AlaPro dipeptides. Active site residues are shown and color coded for clarity. The white line serves as a visual clue for the aligned active sites.(B) Active site views. A portion of FK506 bound to FKBP, and the AlaPro dipeptides bound to Pin1 and CyPA are shown. The psi (ψ) rotation for the alanine in the dipeptide bound to Pin1 relative to the same alanine in the dipeptide bound to CyPA likely occurs to avoid a steric clash between the β-methyl group of alanine and the bound sulfate anion. In Pin1, dashed gray lines emphasize the relationship of Cys-113 and His-59 to the peptide bond of the AlaPro peptide. Both panels were produced with the conic option ([20]) of MIDAS ( [11]).
The above figures are reprinted by permission from Cell Press: Cell (1997, 89, 875-886) copyright 1997.
Secondary reference #1
Title A human peptidyl-Prolyl isomerase essential for regulation of mitosis.
Authors K.P.Lu, S.D.Hanes, T.Hunter.
Ref. Nature, 1996, 380, 544-547.
PubMed id 8606777
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