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Hydrolase/hydrolase inhibitor
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PDB id
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1fjm
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.3.1.3.16
- Phosphoprotein phosphatase.
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Reaction:
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A phosphoprotein + H2O = a protein + phosphate
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phosphoprotein
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+
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H(2)O
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=
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protein
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+
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phosphate
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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PTW/PP1 phosphatase complex
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5 terms
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Biological process
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cell cycle
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4 terms
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Biochemical function
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protein binding
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4 terms
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DOI no:
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Nature
376:745-753
(1995)
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PubMed id:
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Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1.
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J.Goldberg,
H.B.Huang,
Y.G.Kwon,
P.Greengard,
A.C.Nairn,
J.Kuriyan.
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| |
ABSTRACT
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| |
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The crystal structure of mammalian protein phosphatase-1, complexed with the
toxin microcystin and determined at 2.1 A resolution, reveals that it is a
metalloenzyme unrelated in architecture to the tyrosine phosphatases. Two metal
ions are positioned by a central beta-alpha-beta-alpha-beta scaffold at the
active site, from which emanate three surface grooves that are potential binding
sites for substrates and inhibitors. The carboxy terminus is positioned at the
end of one of the grooves such that regulatory sequences following the domain
might modulate function. The fold of the catalytic domain is expected to be
closely preserved in protein phosphatases 2A and 2B (calcineurin).
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Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
D.Ogawa,
K.Abe,
A.Miyao,
M.Kojima,
H.Sakakibara,
M.Mizutani,
H.Morita,
Y.Toda,
T.Hobo,
Y.Sato,
T.Hattori,
H.Hirochika,
and
S.Takeda
(2011).
RSS1 regulates the cell cycle and maintains meristematic activity under stress conditions in rice.
|
| |
Nat Commun, 2,
278.
|
|
|
|
|
|
|
S.R.Pereira,
V.T.Vasconcelos,
and
A.Antunes
(2011).
The phosphoprotein phosphatase family of Ser/Thr phosphatases as principal targets of naturally occurring toxins.
|
| |
Crit Rev Toxicol, 41,
83.
|
|
|
|
|
|
|
A.Campos,
and
V.Vasconcelos
(2010).
Molecular mechanisms of microcystin toxicity in animal cells.
|
| |
Int J Mol Sci, 11,
268-287.
|
|
|
|
|
|
|
A.E.Fagerholm,
D.Habrant,
and
A.M.Koskinen
(2010).
Calyculins and related marine natural products as serine-threonine protein phosphatase PP1 and PP2A inhibitors and total syntheses of calyculin A, B, and C.
|
| |
Mar Drugs, 8,
122-172.
|
|
|
|
|
|
|
A.Hirschi,
M.Cecchini,
R.C.Steinhardt,
M.R.Schamber,
F.A.Dick,
and
S.M.Rubin
(2010).
An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein.
|
| |
Nat Struct Mol Biol, 17,
1051-1057.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
A.Ziková,
A.Trubiroha,
C.Wiegand,
S.Wuertz,
B.Rennert,
S.Pflugmacher,
R.Kopp,
J.Mareš,
P.Spurný,
and
W.Kloas
(2010).
Impact of microcystin containing diets on physiological performance of Nile tilapia (Oreochromis niloticus) concerning detoxification.
|
| |
J Environ Monit, 12,
2276-2281.
|
|
|
|
|
|
|
C.Adám,
L.Henn,
M.Miskei,
M.Erdélyi,
P.Friedrich,
and
V.Dombrádi
(2010).
Conservation of male-specific expression of novel phosphoprotein phosphatases in Drosophila.
|
| |
Dev Genes Evol, 220,
123-128.
|
|
|
|
|
|
|
E.Lance,
M.R.Neffling,
C.Gérard,
J.Meriluoto,
and
M.Bormans
(2010).
Accumulation of free and covalently bound microcystins in tissues of Lymnaea stagnalis (Gastropoda) following toxic cyanobacteria or dissolved microcystin-LR exposure.
|
| |
Environ Pollut, 158,
674-680.
|
|
|
|
|
|
|
I.Sainis,
D.Fokas,
K.Vareli,
A.G.Tzakos,
V.Kounnis,
and
E.Briasoulis
(2010).
Cyanobacterial cyclopeptides as lead compounds to novel targeted cancer drugs.
|
| |
Mar Drugs, 8,
629-657.
|
|
|
|
|
|
|
L.Kovács,
I.Farkas,
L.Majoros,
M.Miskei,
I.Pócsi,
and
V.Dombrádi
(2010).
The polymorphism of protein phosphatase Z1 gene in Candida albicans.
|
| |
J Basic Microbiol, 50,
S74-S82.
|
|
|
|
|
|
|
M.Bollen,
W.Peti,
M.J.Ragusa,
and
M.Beullens
(2010).
The extended PP1 toolkit: designed to create specificity.
|
| |
Trends Biochem Sci, 35,
450-458.
|
|
|
|
|
|
|
M.J.Ragusa,
B.Dancheck,
D.A.Critton,
A.C.Nairn,
R.Page,
and
W.Peti
(2010).
Spinophilin directs protein phosphatase 1 specificity by blocking substrate binding sites.
|
| |
Nat Struct Mol Biol, 17,
459-464.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
A.Khromov,
N.Choudhury,
A.S.Stevenson,
A.V.Somlyo,
and
M.Eto
(2009).
Phosphorylation-dependent Autoinhibition of Myosin Light Chain Phosphatase Accounts for Ca2+ Sensitization Force of Smooth Muscle Contraction.
|
| |
J Biol Chem, 284,
21569-21579.
|
|
|
|
|
|
|
A.Plaza,
G.Bifulco,
J.L.Keffer,
J.R.Lloyd,
H.L.Baker,
and
C.A.Bewley
(2009).
Celebesides A-C and theopapuamides B-D, depsipeptides from an Indonesian sponge that inhibit HIV-1 entry.
|
| |
J Org Chem, 74,
504-512.
|
|
|
|
|
|
|
G.Feng,
E.A.Tanifum,
H.Adams,
A.C.Hengge,
and
N.H.Williams
(2009).
Mechanism and transition state structure of aryl methylphosphonate esters doubly coordinated to a dinuclear cobalt(III) center.
|
| |
J Am Chem Soc, 131,
12771-12779.
|
|
|
|
|
|
|
J.O.Liu
(2009).
Calmodulin-dependent phosphatase, kinases, and transcriptional corepressors involved in T-cell activation.
|
| |
Immunol Rev, 228,
184-198.
|
|
|
|
|
|
|
M.A.Aras,
R.A.Saadi,
and
E.Aizenman
(2009).
Zn2+ regulates Kv2.1 voltage-dependent gating and localization following ischemia.
|
| |
Eur J Neurosci, 30,
2250-2257.
|
|
|
|
|
|
|
M.A.Labine,
and
G.Y.Minuk
(2009).
Cyanobacterial toxins and liver disease.
|
| |
Can J Physiol Pharmacol, 87,
773-788.
|
|
|
|
|
|
|
M.R.Swingle,
L.Amable,
B.G.Lawhorn,
S.B.Buck,
C.P.Burke,
P.Ratti,
K.L.Fischer,
D.L.Boger,
and
R.E.Honkanen
(2009).
Structure-activity relationship studies of fostriecin, cytostatin, and key analogs, with PP1, PP2A, PP5, and( beta12-beta13)-chimeras (PP1/PP2A and PP5/PP2A), provide further insight into the inhibitory actions of fostriecin family inhibitors.
|
| |
J Pharmacol Exp Ther, 331,
45-53.
|
|
|
|
|
|
|
M.S.Kelker,
R.Page,
and
W.Peti
(2009).
Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: a novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors.
|
| |
J Mol Biol, 385,
11-21.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
P.Nicolaou,
and
E.G.Kranias
(2009).
Role of PP1 in the regulation of Ca cycling in cardiac physiology and pathophysiology.
|
| |
Front Biosci, 14,
3571-3585.
|
|
|
|
|
|
|
P.Nicolaou,
R.J.Hajjar,
and
E.G.Kranias
(2009).
Role of protein phosphatase-1 inhibitor-1 in cardiac physiology and pathophysiology.
|
| |
J Mol Cell Cardiol, 47,
365-371.
|
|
|
|
|
|
|
R.Amer,
B.Díez,
and
R.El-Shehawy
(2009).
Diversity of hepatotoxic cyanobacteria in the Nile Delta, Egypt.
|
| |
J Environ Monit, 11,
126-133.
|
|
|
|
|
|
|
W.Guo,
B.Shan,
R.C.Klingsberg,
X.Qin,
and
J.A.Lasky
(2009).
Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition.
|
| |
Am J Physiol Lung Cell Mol Physiol, 297,
L864-L870.
|
|
|
|
|
|
|
X.J.Xie,
W.Huang,
C.Z.Xue,
and
Q.Wei
(2009).
The nonconserved N-terminus of protein phosphatase 2B confers its properties to protein phosphatase 1.
|
| |
IUBMB Life, 61,
178-183.
|
|
|
|
|
|
|
X.J.Xie,
W.Huang,
C.Z.Xue,
and
Q.Wei
(2009).
The N-terminal domain influences the structure and property of protein phosphatase 1.
|
| |
Mol Cell Biochem, 327,
241-246.
|
|
|
|
|
|
|
X.Xie,
W.Huang,
C.Xue,
and
Q.Wei
(2009).
E275 and F276 in beta12-beta13 loop of protein phosphatase-1 resist Mn2+-mediated activation.
|
| |
Biosci Biotechnol Biochem, 73,
801-804.
|
|
|
|
|
|
|
Y.Ren,
Z.X.Wang,
and
Q.Wei
(2009).
Mechanism of activation of Saccharomyces cerevisiae calcineurin by Mn2+.
|
| |
Biol Chem, 390,
1155-1162.
|
|
|
|
|
|
|
Y.Shi
(2009).
Serine/threonine phosphatases: mechanism through structure.
|
| |
Cell, 139,
468-484.
|
|
|
|
|
|
|
B.Dancheck,
A.C.Nairn,
and
W.Peti
(2008).
Detailed structural characterization of unbound protein phosphatase 1 inhibitors.
|
| |
Biochemistry, 47,
12346-12356.
|
|
|
|
|
|
|
B.F.Cravatt,
A.T.Wright,
and
J.W.Kozarich
(2008).
Activity-based protein profiling: from enzyme chemistry to proteomic chemistry.
|
| |
Annu Rev Biochem, 77,
383-414.
|
|
|
|
|
|
|
B.Wang,
P.Zhang,
and
Q.Wei
(2008).
Recent progress on the structure of Ser/Thr protein phosphatases.
|
| |
Sci China C Life Sci, 51,
487-494.
|
|
|
|
|
|
|
C.McWhirter,
E.A.Lund,
E.A.Tanifum,
G.Feng,
Q.I.Sheikh,
A.C.Hengge,
and
N.H.Williams
(2008).
Mechanistic study of protein phosphatase-1 (PP1), a catalytically promiscuous enzyme.
|
| |
J Am Chem Soc, 130,
13673-13682.
|
|
|
|
|
|
|
J.R.Crush,
L.R.Briggs,
J.M.Sprosen,
and
S.N.Nichols
(2008).
Effect of irrigation with lake water containing microcystins on microcystin content and growth of ryegrass, clover, rape, and lettuce.
|
| |
Environ Toxicol, 23,
246-252.
|
|
|
|
|
|
|
K.S.Hadler,
T.Huber,
A.I.Cassady,
J.Weber,
J.Robinson,
A.Burrows,
G.Kelly,
L.W.Guddat,
D.A.Hume,
G.Schenk,
and
J.U.Flanagan
(2008).
Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?
|
| |
BMC Res Notes, 1,
78.
|
|
|
|
|
|
|
M.R.Logan,
T.Nguyen,
N.Szapiel,
J.Knockleby,
H.Por,
M.Zadworny,
M.Neszt,
P.Harrison,
H.Bussey,
C.A.Mandato,
J.Vogel,
and
G.Lesage
(2008).
Genetic interaction network of the Saccharomyces cerevisiae type 1 phosphatase Glc7.
|
| |
BMC Genomics, 9,
336.
|
|
|
|
|
|
|
Y.Xu,
Y.Chen,
P.Zhang,
P.D.Jeffrey,
and
Y.Shi
(2008).
Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation.
|
| |
Mol Cell, 31,
873-885.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
A.Tsuchiya,
E.Tashiro,
M.Yoshida,
and
M.Imoto
(2007).
Involvement of protein phosphatase 2A nuclear accumulation and subsequent inactivation of activator protein-1 in leptomycin B-inhibited cyclin D1 expression.
|
| |
Oncogene, 26,
1522-1532.
|
|
|
|
|
|
|
E.Mills,
H.P.Price,
A.Johner,
J.E.Emerson,
and
D.F.Smith
(2007).
Kinetoplastid PPEF phosphatases: dual acylated proteins expressed in the endomembrane system of Leishmania.
|
| |
Mol Biochem Parasitol, 152,
22-34.
|
|
|
|
|
|
|
I.Farkas,
V.Dombrádi,
M.Miskei,
L.Szabados,
and
C.Koncz
(2007).
Arabidopsis PPP family of serine/threonine phosphatases.
|
| |
Trends Plant Sci, 12,
169-176.
|
|
|
|
|
|
|
J.A.Gibbons,
L.Kozubowski,
K.Tatchell,
and
S.Shenolikar
(2007).
Expression of human protein phosphatase-1 in Saccharomyces cerevisiae highlights the role of phosphatase isoforms in regulating eukaryotic functions.
|
| |
J Biol Chem, 282,
21838-21847.
|
|
|
|
|
|
|
K.L.Howard,
and
G.L.Boyer
(2007).
Adduct simplification in the analysis of cyanobacterial toxins by matrix-assisted laser desorption/ionization mass spectrometry.
|
| |
Rapid Commun Mass Spectrom, 21,
699-706.
|
|
|
|
|
|
|
M.Eto,
J.Kirkbride,
E.Elliott,
S.H.Lo,
and
D.L.Brautigan
(2007).
Association of the tensin N-terminal protein-tyrosine phosphatase domain with the alpha isoform of protein phosphatase-1 in focal adhesions.
|
| |
J Biol Chem, 282,
17806-17815.
|
|
|
|
|
|
|
M.Isobe,
M.Kurono,
K.Tsuboi,
and
A.Takai
(2007).
Synthesis of [18,19,21,22-(13)C4]-labeled tautomycin as an NMR probe of protein phosphatase inhibitor.
|
| |
Chem Asian J, 2,
377-385.
|
|
|
|
|
|
|
M.K.Rantanen,
L.Lehtiö,
L.Rajagopal,
C.E.Rubens,
and
A.Goldman
(2007).
Structure of Streptococcus agalactiae serine/threonine phosphatase. The subdomain conformation is coupled to the binding of a third metal ion.
|
| |
FEBS J, 274,
3128-3137.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
N.Keppetipola,
and
S.Shuman
(2007).
Characterization of the 2',3' cyclic phosphodiesterase activities of Clostridium thermocellum polynucleotide kinase-phosphatase and bacteriophage lambda phosphatase.
|
| |
Nucleic Acids Res, 35,
7721-7732.
|
|
|
|
|
|
|
T.D.Hurley,
J.Yang,
L.Zhang,
K.D.Goodwin,
Q.Zou,
M.Cortese,
A.K.Dunker,
and
A.A.DePaoli-Roach
(2007).
Structural basis for regulation of protein phosphatase 1 by inhibitor-2.
|
| |
J Biol Chem, 282,
28874-28883.
|
|
|
PDB codes:
|
|
|
|
|
|
|
|
U.S.Cho,
and
W.Xu
(2007).
Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme.
|
| |
Nature, 445,
53-57.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
Y.Kim,
M.S.Gentry,
T.E.Harris,
S.E.Wiley,
J.C.Lawrence,
and
J.E.Dixon
(2007).
A conserved phosphatase cascade that regulates nuclear membrane biogenesis.
|
| |
Proc Natl Acad Sci U S A, 104,
6596-6601.
|
|
|
|
|
|
|
A.El-Toukhy,
A.M.Given,
O.Ogut,
and
F.V.Brozovich
(2006).
PHI-1 interacts with the catalytic subunit of myosin light chain phosphatase to produce a Ca(2+) independent increase in MLC(20) phosphorylation and force in avian smooth muscle.
|
| |
FEBS Lett, 580,
5779-5784.
|
|
|
|
|
|
|
A.Rantala,
P.Rajaniemi-Wacklin,
C.Lyra,
L.Lepistö,
J.Rintala,
J.Mankiewicz-Boczek,
and
K.Sivonen
(2006).
Detection of microcystin-producing cyanobacteria in Finnish lakes with genus-specific microcystin synthetase gene E (mcyE) PCR and associations with environmental factors.
|
| |
Appl Environ Microbiol, 72,
6101-6110.
|
|
|
|
|
|
|
E.Dittmann,
and
C.Wiegand
(2006).
Cyanobacterial toxins--occurrence, biosynthesis and impact on human affairs.
|
| |
Mol Nutr Food Res, 50,
7.
|
|
|
|
|
|
|
E.Purev,
A.Giordano,
D.R.Soprano,
and
K.J.Soprano
(2006).
Interaction of PP2A catalytic subunit with Rb2/p130 is required for all-trans retinoic acid suppression of ovarian carcinoma cell growth.
|
| |
J Cell Physiol, 206,
495-502.
|
|
|
|
|
|
|
G.Van Driessche,
B.Devreese,
J.C.Fitch,
T.E.Meyer,
M.A.Cusanovich,
and
J.J.Van Beeumen
(2006).
GHP, a new c-type green heme protein from Halochromatium salexigens and other proteobacteria.
|
| |
FEBS J, 273,
2801-2811.
|
|
|
|
|
|
|
I.S.Ramsey,
M.M.Moran,
J.A.Chong,
and
D.E.Clapham
(2006).
A voltage-gated proton-selective channel lacking the pore domain.
|
| |
Nature, 440,
1213-1216.
|
|
|
|
|
|
|
J.Cazenave,
M.d.e. .L.Bistoni,
E.Zwirnmann,
D.A.Wunderlin,
and
C.Wiegand
(2006).
Attenuating effects of natural organic matter on microcystin toxicity in zebra fish (Danio rerio) embryos -- benefits and costs of microcystin detoxication.
|
| |
Environ Toxicol, 21,
22-32.
|
|
|
|
|
|
|
J.Jordens,
V.Janssens,
S.Longin,
I.Stevens,
E.Martens,
G.Bultynck,
Y.Engelborghs,
E.Lescrinier,
E.Waelkens,
J.Goris,
and
C.Van Hoof
(2006).
The protein phosphatase 2A phosphatase activator is a novel peptidyl-prolyl cis/trans-isomerase.
|
| |
J Biol Chem, 281,
6349-6357.
|
|
|
|
|
|
|
N.Keppetipola,
and
S.Shuman
(2006).
Mechanism of the phosphatase component of Clostridium thermocellum polynucleotide kinase-phosphatase.
|
| |
RNA, 12,
73-82.
|
|
|
|
|
|
|
N.Keppetipola,
and
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J Biol Chem, 271,
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PDB code:
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EMBO J, 15,
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PDB code:
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Eur J Biochem, 239,
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Enzymatic pathway for the bacterial degradation of the cyanobacterial cyclic peptide toxin microcystin LR.
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Appl Environ Microbiol, 62,
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G.B.Trogen,
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Biochemistry, 35,
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PDB code:
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J.Clotet,
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J Biol Chem, 271,
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Identification and characterization of cAMP-dependent protein kinase and its possible direct interactions with protein phosphatase-1 in marine dinoflagellates.
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Biochem Cell Biol, 74,
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Protein phosphatase type 1 interacts with proteins required for meiosis and other cellular processes in Saccharomyces cerevisiae.
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Interactions between a minimal protein serine/threonine phosphatase and its phosphopeptide substrate sequence.
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J Biol Chem, 271,
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