Tautomycin's interactions with protein phosphatase 1.
It has been a long journey since tautomycin (TTM) was isolated in 1987 and the discovery that it inhibited protein phosphatase 1 (PP1) more strongly than PP2A until finally the cocrystal structure of TTM and PP1 was presented early in 2009. The fact that TTM shows preference to inhibit PP1 over PP2A makes this compound unique among the known PP1 and PP2A inhibitors. A number of groups were involved in work aiming to unravel TTM's interactions with PP1 and by doing so hoping to disentangle the secrets as to why TTM is a better inhibitor of PP1 than PP2A. This Focus Review looks back at the work conducted with TTM in order to establish its point of interaction with PP1 prior to X-ray structure. Finally the conclusions before the X-ray structure are compared with the real situation.
Sydnes
Magne O
MO
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan.
Isobe
Minoru
M
D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010975:Platelet Aggregation Inhibitors; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2