DB code: D00152

RLCP classification 1.15.7590.1491 : Hydrolysis
CATH domain 3.60.40.10 : Phosphatase 2c; domain 1 Catalytic domain
1.10.10.430 : Arc Repressor Mutant, subunit A
E.C. 3.1.3.16
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P35813 Protein phosphatase 1A
EC 3.1.3.16
Protein phosphatase 2C isoform alpha
PP2C-alpha
IA
NP_066283.1 (Protein)
NM_021003.4 (DNA/RNA sequence)
NP_808820.1 (Protein)
NM_177951.2 (DNA/RNA sequence)
NP_808821.2 (Protein)
NM_177952.2 (DNA/RNA sequence)
PF00481 (PP2C)
PF07830 (PP2C_C)
[Graphical View]
O75688 Protein phosphatase 1B
EC 3.1.3.16
Protein phosphatase 2C isoform beta
PP2C-beta
NP_001028728.1 (Protein)
NM_001033556.1 (DNA/RNA sequence)
NP_001028729.1 (Protein)
NM_001033557.1 (DNA/RNA sequence)
NP_002697.1 (Protein)
NM_002706.4 (DNA/RNA sequence)
NP_808907.1 (Protein)
NM_177968.2 (DNA/RNA sequence)
NP_808908.1 (Protein)
NM_177969.2 (DNA/RNA sequence)
PF00481 (PP2C)
PF07830 (PP2C_C)
[Graphical View]

KEGG enzyme name
protein phosphatase-2A
phosphoprotein phosphatase
protein phosphatase-1
protein phosphatase-2B
protein phosphatase-2C
protein D phosphatase
phosphospectrin phosphatase
casein phosphatase
Aspergillus awamori acid protein phosphatase
calcineurin
phosphatase 2A
phosphatase 2B
phosphatase II
phosphatase IB
phosphatase C-II
polycation modulated (PCM-) phosphatase
phosphopyruvate dehydrogenase phosphatase
phosphatase SP
branched-chain alpha-keto acid dehydrogenase phosphatase
BCKDH phosphatase
3-hydroxy 3-methylglutaryl coenzymeA reductase phosphatase
HMG-CoA reductase phosphatase
phosphatase H-II
phosphatase III
phosphatase I
protein phosphatase
phosphatase IV

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P35813 PPM1A_HUMAN A phosphoprotein + H(2)O = a protein + phosphate. Monomer. Binds 2 magnesium or manganese ions per subunit.
O75688 PPM1B_HUMAN A phosphoprotein + H(2)O = a protein + phosphate. Monomer (By similarity). Binds 2 magnesium or manganese ions per subunit (By similarity).

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00034 C00305 C00562 C00001 C00017 C00009
E.C.
Compound Manganese Magnesium Phosphoprotein H2O Protein Phosphate
Type heavy metal divalent metal (Ca2+, Mg2+) peptide/protein,phosphate group/phosphate ion H2O peptide/protein phosphate group/phosphate ion
ChEBI 18291
 35154
 18291
 35154
 		18420
 18420
 		15377
 15377
 		26078
 26078
PubChem 23930
 23930
 		888
 888
 		22247451
 962
 22247451
 962
 		1004
 22486802
 1004
 22486802
1a6qA01 Bound:2x_MN Unbound Unbound Bound:HOH_187 Unbound Bound:PO4
2p8eA Unbound Bound:_MG Unbound Unbound Unbound Unbound
2p8eB Unbound Bound:_MG Unbound Unbound Unbound Unbound
1a6qA02 Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1a6q & literature [3], [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a6qA01 ARG 33;HIS 62;ASP 282 ASP 239;ASP 282(Metal-1 binding);ASP 60(both metals binding);GLY 61(Metal-2 binding)
2p8eA ARG 33;HIS 62;ASP 286 ASP 243;ASP 286(Metal-1 binding);ASP 60(both metals binding);GLY 61(Metal-2 binding) OCS 242
2p8eB ARG 33;HIS 62;ASP 286 ASP 243;ASP 286(Metal-1 binding);ASP 60(both metals binding);GLY 61(Metal-2 binding) OCS 242
1a6qA02

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Fig. 6, p.6801-6805
[4]
p.411
[6]
p.147
[9]
Fig.23, p.2334-2336
[12]
Fig.1, Fig.6, p.8518-8520
[14]
Fig.15, p.3350-3351
[15]
Fig.3, p.867-869

References
[1]
Resource
Comments
Medline ID
PubMed ID 2549856
Journal Annu Rev Biochem
Year 1989
Volume 58
Pages 453-508
Authors Cohen P
Title The structure and regulation of protein phosphatases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7575450
Journal Biochem J
Year 1995
Volume 311
Pages 17-29
Authors Wera S, Hemmings BA
Title Serine/threonine protein phosphatases.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)
Medline ID 97157470
PubMed ID 9003755
Journal EMBO J
Year 1996
Volume 15
Pages 6798-809
Authors Das AK, Helps NR, Cohen PT, Barford D
Title Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution.
Related PDB 1a6q
Related UniProtKB P35813
[4]
Resource
Comments
Medline ID
PubMed ID 8987393
Journal Trends Biochem Sci
Year 1996
Volume 21
Pages 407-12
Authors Barford D
Title Molecular mechanisms of the protein serine/threonine phosphatases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9276438
Journal FEBS Lett
Year 1997
Volume 412
Pages 415-9
Authors Travis SM, Welsh MJ
Title PP2C gamma: a human protein phosphatase with a unique acidic domain.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 9646865
Journal Annu Rev Biophys Biomol Struct
Year 1998
Volume 27
Pages 133-64
Authors Barford D, Das AK, Egloff MP
Title The structure and mechanism of protein phosphatases: insights into catalysis and regulation.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10234829
Journal FEMS Microbiol Lett
Year 1999
Volume 174
Pages 117-23
Authors Schroeter R, Schlisio S, Lucet I, Yudkin M, Borriss R
Title The Bacillus subtilis regulator protein SpoIIE shares functional and structural similarities with eukaryotic protein phosphatases 2C.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 10400656
Journal J Biol Chem
Year 1999
Volume 274
Pages 20336-43
Authors Fjeld CC, Denu JM
Title Kinetic analysis of human serine/threonine protein phosphatase 2Calpha.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 11749375
Journal Chem Rev
Year 2001
Volume 101
Pages 2313-40
Authors Jackson MD, Denu JM
Title Molecular reactions of protein phosphatases--insights from structure and chemistry.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11331582
Journal EMBO J
Year 2001
Volume 20
Pages 2160-70
Authors Leung-Hagesteijn C, Mahendra A, Naruszewicz I, Hannigan GE
Title Modulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11734222
Journal FEBS Lett
Year 2001
Volume 509
Pages 142-4
Authors Jiang L, Whiteway M, Shen SH
Title A novel type 2C protein phosphatase from the human fungal pathogen Candida albicans.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12859198
Journal Biochemistry
Year 2003
Volume 42
Pages 8513-21
Authors Jackson MD, Fjeld CC, Denu JM
Title Probing the function of conserved residues in the serine/threonine phosphatase PP2Calpha.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 15530359
Journal Structure
Year 2004
Volume 12
Pages 1947-54
Authors Pullen KE, Ng HL, Sung PY, Good MC, Smith SM, Alber T
Title An alternate conformation and a third metal in PstP/Ppp, the M. tuberculosis PP2C-Family Ser/Thr protein phosphatase.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 16895331
Journal Chem Rev
Year 2006
Volume 106
Pages 3338-63
Authors Mitic N, Smith SJ, Neves A, Guddat LW, Gahan LR, Schenk G
Title The catalytic mechanisms of binuclear metallohydrolases.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 16509582
Journal J Med Chem
Year 2006
Volume 49
Pages 1658-67
Authors Rogers JP, Beuscher AE 4th, Flajolet M, McAvoy T, Nairn AC, Olson AJ, Greengard P
Title Discovery of protein phosphatase 2C inhibitors by virtual screening.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 17637345
Journal Structure
Year 2007
Volume 15
Pages 863-72
Authors Bellinzoni M, Wehenkel A, Shepard W, Alzari PM
Title Insights into the catalytic mechanism of PPM Ser/Thr phosphatases from the atomic resolution structures of a mycobacterial enzyme.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 18058037
Journal J Struct Funct Genomics
Year 2007
Volume 8
Pages 121-40
Authors Almo SC, Bonanno JB, Sauder JM, Emtage S, Dilorenzo TP, Malashkevich V, Wasserman SR, Swaminathan S, Eswaramoorthy S, Agarwal R, Kumaran D, Madegowda M, Ragumani S, Patskovsky Y, Alvarado J, Ramagopal UA, Faber-Barata J, Chance MR, Sali A, Fiser A, Zhang ZY, Lawrence DS, Burley SK
Title Structural genomics of protein phosphatases.
Related PDB 2p8e
Related UniProtKB

Comments
Enzymes with EC 3.1.3.16 belong to several superfamilies. This enzyme belongs to protein phosphatase 2C (PP2C) family, and the PPM superfamily.
This enzyme catalyzes the following reaction (see [3], [12]):
(1) Asp282 acts as a general base to activate the bridging water, bound to both the metal ions, which should be the nucleophile.
(2) The activated water (or hydroxide ion) makes a nucleophilic attack on the phosphorus atom of the substrate in a SN2-mechanism.
(3) The transition state must be stabilized by Arg33.
(4) His62 may act as a general acid to protonate the leaving group, oxygen atom.

Created Updated
2004-11-22 2009-02-26