-
Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent.
Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
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.
PMID: 9200606 [PubMed - indexed for MEDLINE]
-
Cited by 58 PubMed Central articles
-
Molecular and Biochemical Characterization of the Parvulin-Type PPIases in Lotus japonicus.
Kouri ED, Labrou NE, Garbis SD, Kalliampakou KI, Stedel C, Dimou M, Udvardi MK, Katinakis P, Flemetakis E.
Plant Physiol. 2009 Jul; 150(3):1160-73. Epub 2009 Apr 29.
[Plant Physiol. 2009]
-
Solution structure of the parvulin-type PPIase domain of Staphylococcus aureus PrsA--implications for the catalytic mechanism of parvulins.
Heikkinen O, Seppala R, Tossavainen H, Heikkinen S, Koskela H, Permi P, Kilpeläinen I.
BMC Struct Biol. 2009 Mar 24; 9:17. Epub 2009 Mar 24.
[BMC Struct Biol. 2009]
-
Detection of protein catalytic residues at high precision using local network properties.
Slama P, Filippis I, Lappe M.
BMC Bioinformatics. 2008 Dec 4; 9:517. Epub 2008 Dec 4.
[BMC Bioinformatics. 2008]
- » See all...
Structures reported by this article
Patient Drug Information
-
Tacrolimus (Prograf® )
Tacrolimus is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received kidney, liver, or heart transplants. ...