PDBsum entry 1l7o

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Jmol PyMol
Protein chains
200 a.a. *
ACY ×2
_ZN ×3
Waters ×140
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of phosphoserine phosphatase in apo form
Structure: Phosphoserine phosphatase. Chain: a, b. Synonym: psp, o-phosphoserine phosphohydrolase, pspase. Engineered: yes. Mutation: yes
Source: Methanocaldococcus jannaschii. Organism_taxid: 2190. Gene: mj1594. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.20Å     R-factor:   0.224     R-free:   0.254
Authors: W.Wang,H.S.Cho,R.Kim,J.Jancarik,H.Yokota,H.H.Nguyen,I.V.Grig D.E.Wemmer,S.H.Kim,Berkeley Structural Genomics Center (Bsg
Key ref:
W.Wang et al. (2002). Structural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic "snapshots" of intermediate states. J Mol Biol, 319, 421-431. PubMed id: 12051918 DOI: 10.1016/S0022-2836(02)00324-8
16-Mar-02     Release date:   19-Jun-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q58989  (SERB_METJA) -  Phosphoserine phosphatase
211 a.a.
200 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Phosphoserine phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: O-phospho-L(or D)-serine + H2O = L(or D)-serine + phosphate
O-phospho-L(or D)-serine
+ H(2)O
= L(or D)-serine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dephosphorylation   3 terms 
  Biochemical function     hydrolase activity     3 terms  


    Key reference    
DOI no: 10.1016/S0022-2836(02)00324-8 J Mol Biol 319:421-431 (2002)
PubMed id: 12051918  
Structural characterization of the reaction pathway in phosphoserine phosphatase: crystallographic "snapshots" of intermediate states.
W.Wang, H.S.Cho, R.Kim, J.Jancarik, H.Yokota, H.H.Nguyen, I.V.Grigoriev, D.E.Wemmer, S.H.Kim.
Phosphoserine phosphatase (PSP) is a member of a large class of enzymes that catalyze phosphoester hydrolysis using a phosphoaspartate-enzyme intermediate. PSP is a likely regulator of the steady-state d-serine level in the brain, which is a critical co-agonist of the N-methyl-d-aspartate type of glutamate receptors. Here, we present high-resolution (1.5-1.9 A) structures of PSP from Methanococcus jannaschii, which define the open state prior to substrate binding, the complex with phosphoserine substrate bound (with a D to N mutation in the active site), and the complex with AlF3, a transition-state analog for the phospho-transfer steps in the reaction. These structures, together with those described for the BeF3- complex (mimicking the phospho-enzyme) and the enzyme with phosphate product in the active site, provide a detailed structural picture of the full reaction cycle. The structure of the apo state indicates partial unfolding of the enzyme to allow substrate binding, with refolding in the presence of substrate to provide specificity. Interdomain and active-site conformational changes are identified. The structure with the transition state analog bound indicates a "tight" intermediate. A striking structure homology, with significant sequence conservation, among PSP, P-type ATPases and response regulators suggests that the knowledge of the PSP reaction mechanism from the structures determined will provide insights into the reaction mechanisms of the other enzymes in this family.
  Selected figure(s)  
Figure 3.
Figure 3. PSP structure: (a) a ribbon diagram; (b) a topology diagram.
Figure 5.
Figure 5. Structural "snapshots" of the PSP reaction cycle in the active site. (a) The PSP reaction cycle. (b) Structure and models in the active site. (I) The apo-enzyme structure. (II) The substrate, PLS, bound structure, using mutant D11N. (III) The model of Ser bound transition state structural analogue. A Ser molecule was modeled in the AlF[3]-PSP active site. (IV) Phospho-aspartyl enzyme intermediate structural analogue. The PSP+BeF[3]^ - complex. (V) The transition state structural analogue. AlF[3]-PSP complex. (VI) The product, Pi, bound structure.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 319, 421-431) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21223544 P.Wei, L.C.Milbauer, J.Enenstein, J.Nguyen, W.Pan, and R.P.Hebbel (2011).
Differential endothelial cell gene expression by African Americans versus Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer.
  BMC Med, 9, 2.  
20652880 S.Re, T.Imai, J.Jung, S.Ten-No, and Y.Sugita (2011).
Geometrically associative yet electronically dissociative character in the transition state of enzymatic reversible phosphorylation.
  J Comput Chem, 32, 260-270.  
20050614 H.H.Nguyen, L.Wang, H.Huang, E.Peisach, D.Dunaway-Mariano, and K.N.Allen (2010).
Structural determinants of substrate recognition in the HAD superfamily member D-glycero-D-manno-heptose-1,7-bisphosphate phosphatase (GmhB) .
  Biochemistry, 49, 1082-1092.
PDB codes: 3l8e 3l8f 3l8g 3l8h
20118641 H.Suzuki, K.Yamasaki, T.Daiho, and S.Danko (2010).
[Mechanism of ca(2+) pump as revealed by mutations, development of stable analogs of phosphorylated intermediates, and their structural analyses].
  Yakugaku Zasshi, 130, 179-189.  
20809990 J.V.Møller, C.Olesen, A.M.Winther, and P.Nissen (2010).
The sarcoplasmic Ca2+-ATPase: design of a perfect chemi-osmotic pump.
  Q Rev Biophys, 43, 501-566.  
20211578 R.B.Bourret (2010).
Receiver domain structure and function in response regulator proteins.
  Curr Opin Microbiol, 13, 142-149.  
20080618 Y.Pazy, M.A.Motaleb, M.T.Guarnieri, N.W.Charon, R.Zhao, and R.E.Silversmith (2010).
Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate.
  Proc Natl Acad Sci U S A, 107, 1924-1929.
PDB code: 3hzh
19154134 J.Dai, L.Finci, C.Zhang, S.Lahiri, G.Zhang, E.Peisach, K.N.Allen, and D.Dunaway-Mariano (2009).
Analysis of the structural determinants underlying discrimination between substrate and solvent in beta-phosphoglucomutase catalysis.
  Biochemistry, 48, 1984-1995.
PDB code: 3fm9
19923713 K.O.Håkansson (2009).
The structure of Mg-ATPase nucleotide-binding domain at 1.6 A resolution reveals a unique ATP-binding motif.
  Acta Crystallogr D Biol Crystallogr, 65, 1181-1186.
PDB code: 3gwi
19340413 M.Decker, M.Arand, and A.Cronin (2009).
Mammalian epoxide hydrolases in xenobiotic metabolism and signalling.
  Arch Toxicol, 83, 297-318.  
19561071 S.Danko, T.Daiho, K.Yamasaki, X.Liu, and H.Suzuki (2009).
Formation of the stable structural analog of ADP-sensitive phosphoenzyme of Ca2+-ATPase with occluded Ca2+ by beryllium fluoride: structural changes during phosphorylation and isomerization.
  J Biol Chem, 284, 22722-22735.  
19672539 S.Michielssens, N.Tien Trung, M.Froeyen, P.Herdewijn, M.Tho Nguyen, and A.Ceulemans (2009).
Hydrolysis of aspartic acid phosphoramidate nucleotides: a comparative quantum chemical study.
  Phys Chem Chem Phys, 11, 7274-7285.  
19646451 Y.Pazy, A.C.Wollish, S.A.Thomas, P.J.Miller, E.J.Collins, R.B.Bourret, and R.E.Silversmith (2009).
Matching biochemical reaction kinetics to the timescales of life: structural determinants that influence the autodephosphorylation rate of response regulator proteins.
  J Mol Biol, 392, 1205-1220.
PDB codes: 3f7n 3fft 3ffw 3ffx 3fgz
19026779 A.Ghosh, S.Shuman, and C.D.Lima (2008).
The structure of Fcp1, an essential RNA polymerase II CTD phosphatase.
  Mol Cell, 32, 478-490.
PDB codes: 3ef0 3ef1
18557815 S.A.Thomas, J.A.Brewster, and R.B.Bourret (2008).
Two variable active site residues modulate response regulator phosphoryl group stability.
  Mol Microbiol, 69, 453-465.  
19018103 T.Kawamura, N.Watanabe, and I.Tanaka (2008).
Structure of mannosyl-3-phosphoglycerate phosphatase from Pyrococcus horikoshii.
  Acta Crystallogr D Biol Crystallogr, 64, 1267-1276.
PDB codes: 1wzc 2zos
18398008 Z.Lu, D.Dunaway-Mariano, and K.N.Allen (2008).
The catalytic scaffold of the haloalkanoic acid dehalogenase enzyme superfamily acts as a mold for the trigonal bipyramidal transition state.
  Proc Natl Acad Sci U S A, 105, 5687-5692.
PDB codes: 2rar 2rav 2rb5 2rbk
17154432 A.K.Hirsch, F.R.Fischer, and F.Diederich (2007).
Phosphate recognition in structural biology.
  Angew Chem Int Ed Engl, 46, 338-352.  
18077416 C.Toyoshima, Y.Norimatsu, S.Iwasawa, T.Tsuda, and H.Ogawa (2007).
How processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump.
  Proc Natl Acad Sci U S A, 104, 19831-19836.
PDB codes: 2zbe 2zbf 2zbg
17654724 Q.Xu, K.S.Saikatendu, S.S.Krishna, D.McMullan, P.Abdubek, S.Agarwalla, E.Ambing, T.Astakhova, H.L.Axelrod, D.Carlton, H.J.Chiu, T.Clayton, M.DiDonato, L.Duan, M.A.Elsliger, J.Feuerhelm, S.K.Grzechnik, J.Hale, E.Hampton, G.W.Han, J.Haugen, L.Jaroszewski, K.K.Jin, H.E.Klock, M.W.Knuth, E.Koesema, M.D.Miller, A.T.Morse, E.Nigoghossian, L.Okach, S.Oommachen, J.Paulsen, R.Reyes, C.L.Rife, R.Schwarzenbacher, H.van den Bedem, A.White, G.Wolf, K.O.Hodgson, J.Wooley, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2007).
Crystal structure of MtnX phosphatase from Bacillus subtilis at 2.0 A resolution provides a structural basis for bipartite phosphomonoester hydrolysis of 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate.
  Proteins, 69, 433-439.
PDB code: 2fea
17581653 S.C.Kamerlin, and J.Wilkie (2007).
The role of metal ions in phosphate ester hydrolysis.
  Org Biomol Chem, 5, 2098-2108.  
17071763 S.Helgadóttir, G.Rosas-Sandoval, D.Söll, and D.E.Graham (2007).
Biosynthesis of phosphoserine in the Methanococcales.
  J Bacteriol, 189, 575-582.  
17616523 Y.Hatori, E.Majima, T.Tsuda, and C.Toyoshima (2007).
Domain organization and movements in heavy metal ion pumps: papain digestion of CopA, a Cu+-transporting ATPase.
  J Biol Chem, 282, 25213-25221.  
16672222 E.Bitto, C.A.Bingman, G.E.Wesenberg, J.G.McCoy, and G.N.Phillips (2006).
Structure of pyrimidine 5'-nucleotidase type 1. Insight into mechanism of action and inhibition during lead poisoning.
  J Biol Chem, 281, 20521-20529.
PDB codes: 2bdu 2g06 2g07 2g08 2g09 2g0a
16628247 E.S.Groban, A.Narayanan, and M.P.Jacobson (2006).
Conformational changes in protein loops and helices induced by post-translational phosphorylation.
  PLoS Comput Biol, 2, e32.  
16966333 E.S.Rangarajan, A.Proteau, J.Wagner, M.N.Hung, A.Matte, and M.Cygler (2006).
Structural snapshots of Escherichia coli histidinol phosphate phosphatase along the reaction pathway.
  J Biol Chem, 281, 37930-37941.
PDB codes: 2fpr 2fps 2fpu 2fpw 2fpx
16449230 J.D.Clausen, D.B.McIntosh, D.G.Woolley, A.N.Anthonisen, B.Vilsen, and J.P.Andersen (2006).
Asparagine 706 and glutamate 183 at the catalytic site of sarcoplasmic reticulum Ca2+-ATPase play critical but distinct roles in E2 states.
  J Biol Chem, 281, 9471-9481.  
16815921 K.N.Rao, D.Kumaran, J.Seetharaman, J.B.Bonanno, S.K.Burley, and S.Swaminathan (2006).
Crystal structure of trehalose-6-phosphate phosphatase-related protein: biochemical and biological implications.
  Protein Sci, 15, 1735-1744.
PDB code: 1u02
16540464 N.R.Silvaggi, C.Zhang, Z.Lu, J.Dai, D.Dunaway-Mariano, and K.N.Allen (2006).
The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a.
  J Biol Chem, 281, 14918-14926.
PDB codes: 2fuc 2fue
  18404470 P.L.Ipata, and M.G.Tozzi (2006).
Recent advances in structure and function of cytosolic IMP-GMP specific 5'-nucleotidase II (cN-II).
  Purinergic Signal, 2, 669-675.  
17106798 P.R.Beassoni, L.H.Otero, M.J.Massimelli, A.T.Lisa, and C.E.Domenech (2006).
Critical active-site residues identified by site-directed mutagenesis in Pseudomonas aeruginosa phosphorylcholine phosphatase, a new member of the haloacid dehalogenases hydrolase superfamily.
  Curr Microbiol, 53, 534-539.  
17070898 S.D.Lahiri, G.Zhang, D.Dunaway-Mariano, and K.N.Allen (2006).
Diversification of function in the haloacid dehalogenase enzyme superfamily: The role of the cap domain in hydrolytic phosphoruscarbon bond cleavage.
  Bioorg Chem, 34, 394-409.
PDB codes: 2iof 2ioh
15657928 A.Roberts, S.Y.Lee, E.McCullagh, R.E.Silversmith, and D.E.Wemmer (2005).
YbiV from Escherichia coli K12 is a HAD phosphatase.
  Proteins, 58, 790-801.
PDB codes: 1rlm 1rlo 1rlt
  16511085 H.Wang, H.Pang, Y.Ding, Y.Li, X.Wu, and Z.Rao (2005).
Purification, crystallization and preliminary X-ray diffraction analysis of human enolase-phosphatase E1.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 521-523.  
15574410 M.Toustrup-Jensen, and B.Vilsen (2005).
Interaction between the catalytic site and the A-M3 linker stabilizes E2/E2P conformational states of Na+,K+-ATPase.
  J Biol Chem, 280, 10210-10218.  
15183870 A.M.Ahmed, and T.Shimamoto (2004).
A plasmid-encoded class 1 integron carrying sat, a putative phosphoserine phosphatase gene and aadA2 from enterotoxigenic Escherichia coli O159 isolated in Japan.
  FEMS Microbiol Lett, 235, 243-248.  
15189143 C.Toyoshima, and G.Inesi (2004).
Structural basis of ion pumping by Ca2+-ATPase of the sarcoplasmic reticulum.
  Annu Rev Biochem, 73, 269-292.  
15448704 C.Toyoshima, H.Nomura, and T.Tsuda (2004).
Lumenal gating mechanism revealed in calcium pump crystal structures with phosphate analogues.
  Nature, 432, 361-368.
PDB codes: 1wpg 2zbd
15229613 C.Toyoshima, and T.Mizutani (2004).
Crystal structure of the calcium pump with a bound ATP analogue.
  Nature, 430, 529-535.
PDB code: 1vfp
15133025 D.B.McIntosh, J.D.Clausen, D.G.Woolley, D.H.MacLennan, B.Vilsen, and J.P.Andersen (2004).
Roles of conserved P domain residues and Mg2+ in ATP binding in the ground and Ca2+-activated states of sarcoplasmic reticulum Ca2+-ATPase.
  J Biol Chem, 279, 32515-32523.  
15331784 D.H.Shin, Y.Lou, J.Jancarik, H.Yokota, R.Kim, and S.H.Kim (2004).
Crystal structure of YjeQ from Thermotoga maritima contains a circularly permuted GTPase domain.
  Proc Natl Acad Sci U S A, 101, 13198-13203.
PDB code: 1u0l
15146493 E.C.Meng, B.J.Polacco, and P.C.Babbitt (2004).
Superfamily active site templates.
  Proteins, 55, 962-976.  
15150270 G.Inesi, H.Ma, D.Lewis, and C.Xu (2004).
Ca2+ occlusion and gating function of Glu309 in the ADP-fluoroaluminate analog of the Ca2+-ATPase phosphoenzyme intermediate.
  J Biol Chem, 279, 31629-31637.  
15056675 H.Zhu, S.Yin, and S.Shuman (2004).
Characterization of polynucleotide kinase/phosphatase enzymes from Mycobacteriophages omega and Cjw1 and vibriophage KVP40.
  J Biol Chem, 279, 26358-26369.  
14970331 J.D.Clausen, B.Vilsen, D.B.McIntosh, A.P.Einholm, and J.P.Andersen (2004).
Glutamate-183 in the conserved TGES motif of domain A of sarcoplasmic reticulum Ca2+-ATPase assists in catalysis of E2/E2P partial reactions.
  Proc Natl Acad Sci U S A, 101, 2776-2781.  
15606776 S.Allegrini, A.Scaloni, M.G.Careddu, G.Cuccu, C.D'Ambrosio, R.Pesi, M.Camici, L.Ferrara, and M.G.Tozzi (2004).
Mechanistic studies on bovine cytosolic 5'-nucleotidase II, an enzyme belonging to the HAD superfamily.
  Eur J Biochem, 271, 4881-4891.  
14754887 S.Danko, K.Yamasaki, T.Daiho, and H.Suzuki (2004).
Distinct natures of beryllium fluoride-bound, aluminum fluoride-bound, and magnesium fluoride-bound stable analogues of an ADP-insensitive phosphoenzyme intermediate of sarcoplasmic reticulum Ca2+-ATPase: changes in catalytic and transport sites during phosphoenzyme hydrolysis.
  J Biol Chem, 279, 14991-14998.  
14701811 S.Hausmann, H.Erdjument-Bromage, and S.Shuman (2004).
Schizosaccharomyces pombe carboxyl-terminal domain (CTD) phosphatase Fcp1: distributive mechanism, minimal CTD substrate, and active site mapping.
  J Biol Chem, 279, 10892-10900.  
14699121 S.K.Singh, K.Yang, S.Karthikeyan, T.Huynh, X.Zhang, M.A.Phillips, and H.Zhang (2004).
The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a novel phosphoserine:homoserine phosphotransferase activity.
  J Biol Chem, 279, 13166-13173.
PDB codes: 1rku 1rkv
14555659 Y.Kim, A.F.Yakunin, E.Kuznetsova, X.Xu, M.Pennycooke, J.Gu, F.Cheung, M.Proudfoot, C.H.Arrowsmith, A.Joachimiak, A.M.Edwards, and D.Christendat (2004).
Structure- and function-based characterization of a new phosphoglycolate phosphatase from Thermoplasma acidophilum.
  J Biol Chem, 279, 517-526.
PDB code: 1l6r
15291819 Y.Peeraer, A.Rabijns, J.F.Collet, E.Van Schaftingen, and C.De Ranter (2004).
How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase.
  Eur J Biochem, 271, 3421-3427.  
  12763767 C.Toyoshima, H.Nomura, and Y.Sugita (2003).
Crystal structures of Ca2+-ATPase in various physiological states.
  Ann N Y Acad Sci, 986, 1-8.  
12824492 D.H.Shin, A.Roberts, J.Jancarik, H.Yokota, R.Kim, D.E.Wemmer, and S.H.Kim (2003).
Crystal structure of a phosphatase with a unique substrate binding domain from Thermotoga maritima.
  Protein Sci, 12, 1464-1472.
PDB code: 1nf2
12598367 D.L.Stokes, and N.M.Green (2003).
Structure and function of the calcium pump.
  Annu Rev Biophys Biomol Struct, 32, 445-468.  
12750373 H.Ma, G.Inesi, and C.Toyoshima (2003).
Substrate-induced conformational fit and headpiece closure in the Ca2+ATPase (SERCA).
  J Biol Chem, 278, 28938-28943.  
12531906 M.Toustrup-Jensen, and B.Vilsen (2003).
Importance of conserved Thr214 in domain A of the Na+,K+ -ATPase for stabilization of the phosphoryl transition state complex in E2P dephosphorylation.
  J Biol Chem, 278, 11402-11410.  
14501135 R.D.Makde, V.Kumar, G.D.Gupta, J.Jasti, T.P.Singh, and S.K.Mahajan (2003).
Expression, purification, crystallization and preliminary X-ray diffraction studies of recombinant class B non-specific acid phosphatase of Salmonella typhimurium.
  Acta Crystallogr D Biol Crystallogr, 59, 1849-1852.  
12591865 R.E.Silversmith, G.P.Guanga, L.Betts, C.Chu, R.Zhao, and R.B.Bourret (2003).
CheZ-mediated dephosphorylation of the Escherichia coli chemotaxis response regulator CheY: role for CheY glutamate 89.
  J Bacteriol, 185, 1495-1502.
PDB code: 1mih
12556522 S.Hausmann, and S.Shuman (2003).
Defining the active site of Schizosaccharomyces pombe C-terminal domain phosphatase Fcp1.
  J Biol Chem, 278, 13627-13632.  
14628042 X.Li, K.A.Oghi, J.Zhang, A.Krones, K.T.Bush, C.K.Glass, S.K.Nigam, A.K.Aggarwal, R.Maas, D.W.Rose, and M.G.Rosenfeld (2003).
Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis.
  Nature, 426, 247-254.  
12777757 Y.Peeraer, A.Rabijns, C.Verboven, J.F.Collet, E.Van Schaftingen, and C.De Ranter (2003).
High-resolution structure of human phosphoserine phosphatase in open conformation.
  Acta Crystallogr D Biol Crystallogr, 59, 971-977.
PDB code: 1nnl
12213811 H.Y.Kim, Y.S.Heo, J.H.Kim, M.H.Park, J.Moon, E.Kim, D.Kwon, J.Yoon, D.Shin, E.J.Jeong, S.Y.Park, T.G.Lee, Y.H.Jeon, S.Ro, J.M.Cho, and K.Y.Hwang (2002).
Molecular basis for the local conformational rearrangement of human phosphoserine phosphatase.
  J Biol Chem, 277, 46651-46658.
PDB codes: 1l8l 1l8o
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.