EzCatDB: D00152
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DB codeD00152
RLCP classification1.15.7590.1491 : Hydrolysis
CATH domainDomain 13.60.40.10 : Phosphatase 2c; domain 1Catalytic domain
Domain 21.10.10.430 : Arc Repressor Mutant, subunit A
E.C.3.1.3.16


Enzyme Name
UniProtKBKEGG

P35813O75688
Protein nameProtein phosphatase 1AProtein phosphatase 1Bphosphoprotein phosphatase
protein phosphatase-1
protein phosphatase-2A
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
SynonymsEC 3.1.3.16
Protein phosphatase 2C isoform alpha
PP2C-alpha
IA
EC 3.1.3.16
Protein phosphatase 2C isoform beta
PP2C-beta
RefSeqNP_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)
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)
PfamPF00481 (PP2C)
PF07830 (PP2C_C)
[Graphical view]
PF00481 (PP2C)
PF07830 (PP2C_C)
[Graphical view]


UniProtKB:Accession NumberP35813O75688
Entry namePPM1A_HUMANPPM1B_HUMAN
ActivityA phosphoprotein + H(2)O = a protein + phosphate.A phosphoprotein + H(2)O = a protein + phosphate.
SubunitMonomer.Monomer (By similarity).
Subcellular location

CofactorBinds 2 magnesium or manganese ions per subunit.Binds 2 magnesium or manganese ions per subunit (By similarity).

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00034C00305C00562C00001C00017C00009
CompoundManganeseMagnesiumPhosphoproteinH2OProteinPhosphate
Typeheavy metaldivalent metal (Ca2+, Mg2+)peptide/protein,phosphate group/phosphate ionH2Opeptide/proteinphosphate group/phosphate ion
ChEBI18291
35154
18420

15377

26078
PubChem23930
888

962
22247451

22486802
1004
              
1a6qA01Bound:2x_MNUnboundUnboundBound:HOH 187UnboundBound:PO4
2p8eAUnboundBound:_MGUnboundUnboundUnboundUnbound
2p8eBUnboundBound:_MGUnboundUnboundUnboundUnbound
1a6qA02UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
PDB;1a6q & literature [3], [12]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
           
1a6qA01ARG 33;HIS 62;ASP 282
ASP 239;ASP 282(Metal-1 binding);ASP 60(both metals binding);GLY 61(Metal-2 binding)
 
2p8eAARG 33;HIS 62;ASP 286
ASP 243;ASP 286(Metal-1 binding);ASP 60(both metals binding);GLY 61(Metal-2 binding)
OCS 242
2p8eBARG 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
ReferencesSectionsNo. 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]
PubMed ID2549856
JournalAnnu Rev Biochem
Year1989
Volume58
Pages453-508
AuthorsCohen P
TitleThe structure and regulation of protein phosphatases.
[2]
PubMed ID7575450
JournalBiochem J
Year1995
Volume311
Pages17-29
AuthorsWera S, Hemmings BA
TitleSerine/threonine protein phosphatases.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)
Medline ID97157470
PubMed ID9003755
JournalEMBO J
Year1996
Volume15
Pages6798-809
AuthorsDas AK, Helps NR, Cohen PT, Barford D
TitleCrystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution.
Related PDB1a6q
Related UniProtKBP35813
[4]
PubMed ID8987393
JournalTrends Biochem Sci
Year1996
Volume21
Pages407-12
AuthorsBarford D
TitleMolecular mechanisms of the protein serine/threonine phosphatases.
[5]
PubMed ID9276438
JournalFEBS Lett
Year1997
Volume412
Pages415-9
AuthorsTravis SM, Welsh MJ
TitlePP2C gamma: a human protein phosphatase with a unique acidic domain.
[6]
PubMed ID9646865
JournalAnnu Rev Biophys Biomol Struct
Year1998
Volume27
Pages133-64
AuthorsBarford D, Das AK, Egloff MP
TitleThe structure and mechanism of protein phosphatases: insights into catalysis and regulation.
[7]
PubMed ID10234829
JournalFEMS Microbiol Lett
Year1999
Volume174
Pages117-23
AuthorsSchroeter R, Schlisio S, Lucet I, Yudkin M, Borriss R
TitleThe Bacillus subtilis regulator protein SpoIIE shares functional and structural similarities with eukaryotic protein phosphatases 2C.
[8]
PubMed ID10400656
JournalJ Biol Chem
Year1999
Volume274
Pages20336-43
AuthorsFjeld CC, Denu JM
TitleKinetic analysis of human serine/threonine protein phosphatase 2Calpha.
[9]
PubMed ID11749375
JournalChem Rev
Year2001
Volume101
Pages2313-40
AuthorsJackson MD, Denu JM
TitleMolecular reactions of protein phosphatases--insights from structure and chemistry.
[10]
PubMed ID11331582
JournalEMBO J
Year2001
Volume20
Pages2160-70
AuthorsLeung-Hagesteijn C, Mahendra A, Naruszewicz I, Hannigan GE
TitleModulation of integrin signal transduction by ILKAP, a protein phosphatase 2C associating with the integrin-linked kinase, ILK1.
[11]
PubMed ID11734222
JournalFEBS Lett
Year2001
Volume509
Pages142-4
AuthorsJiang L, Whiteway M, Shen SH
TitleA novel type 2C protein phosphatase from the human fungal pathogen Candida albicans.
[12]
PubMed ID12859198
JournalBiochemistry
Year2003
Volume42
Pages8513-21
AuthorsJackson MD, Fjeld CC, Denu JM
TitleProbing the function of conserved residues in the serine/threonine phosphatase PP2Calpha.
[13]
PubMed ID15530359
JournalStructure
Year2004
Volume12
Pages1947-54
AuthorsPullen KE, Ng HL, Sung PY, Good MC, Smith SM, Alber T
TitleAn alternate conformation and a third metal in PstP/Ppp, the M. tuberculosis PP2C-Family Ser/Thr protein phosphatase.
[14]
PubMed ID16895331
JournalChem Rev
Year2006
Volume106
Pages3338-63
AuthorsMitic N, Smith SJ, Neves A, Guddat LW, Gahan LR, Schenk G
TitleThe catalytic mechanisms of binuclear metallohydrolases.
[15]
PubMed ID16509582
JournalJ Med Chem
Year2006
Volume49
Pages1658-67
AuthorsRogers JP, Beuscher AE 4th, Flajolet M, McAvoy T, Nairn AC, Olson AJ, Greengard P
TitleDiscovery of protein phosphatase 2C inhibitors by virtual screening.
[16]
PubMed ID17637345
JournalStructure
Year2007
Volume15
Pages863-72
AuthorsBellinzoni M, Wehenkel A, Shepard W, Alzari PM
TitleInsights into the catalytic mechanism of PPM Ser/Thr phosphatases from the atomic resolution structures of a mycobacterial enzyme.
[17]
PubMed ID18058037
JournalJ Struct Funct Genomics
Year2007
Volume8
Pages121-40
AuthorsAlmo 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
TitleStructural genomics of protein phosphatases.
Related PDB2p8e

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.

createdupdated
2004-11-222009-02-26


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