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PDBsum entry 1z12

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protein ligands links
Hydrolase PDB id
1z12
Jmol
Contents
Protein chain
157 a.a. *
Ligands
VO4
* Residue conservation analysis
PDB id:
1z12
Name: Hydrolase
Title: Crystal structure of bovine low molecular weight ptpase complexed with vanadate
Structure: Low molecular weight phosphotyrosine protein phosphatase. Chain: a. Synonym: low molecular weight cytosolic acid phosphatase, ptpase. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: acp1. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.20Å     R-factor:   0.173    
Authors: M.Zhang,M.Zhou,R.L.Van Etten,C.V.Stauffacher
Key ref:
M.Zhang et al. (1997). Crystal structure of bovine low molecular weight phosphotyrosyl phosphatase complexed with the transition state analog vanadate. Biochemistry, 36, 15-23. PubMed id: 8993313 DOI: 10.1021/bi961804n
Date:
03-Mar-05     Release date:   05-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11064  (PPAC_BOVIN) -  Low molecular weight phosphotyrosine protein phosphatase
Seq:
Struc:
158 a.a.
157 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.3.1.3.2  - Acid phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A phosphate monoester + H2O = an alcohol + phosphate
phosphate monoester
+ H(2)O
= alcohol
+ phosphate
   Enzyme class 3: E.C.3.1.3.48  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     peptidyl-tyrosine dephosphorylation   2 terms 
  Biochemical function     hydrolase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi961804n Biochemistry 36:15-23 (1997)
PubMed id: 8993313  
 
 
Crystal structure of bovine low molecular weight phosphotyrosyl phosphatase complexed with the transition state analog vanadate.
M.Zhang, M.Zhou, R.L.Van Etten, C.V.Stauffacher.
 
  ABSTRACT  
 
The early transition metal oxoanions vanadate, molybdate, and tungstate are widely used inhibitors for phosphatase enzymes. These oxoanions could inhibit such enzymes by simply mimicking the tetrahedral geometry of phosphate ion. However, in some cases, the enzyme-inhibitor dissociation constants (Ki) for these oxoanions are much lower than that for phosphate. Such observations gave rise to the hypothesis that in some cases these transition metal oxoanions may inhibit phosphomonoesterases by forming complexes that resemble the trigonal bipyramidal geometry of the SN2(P) transition state. As a test of this, the crystal structures of a low molecular weight protein tyrosine phosphatase at pH 7.5 complexed with the inhibitors vanadate and molybdate were solved at 2.2 A resolution and compared to a newly refined 1.9 A structure of the enzyme. Geometric restraints on the oxoanions were relaxed during refinement in order to minimize model bias. Both inhibitors were bound at the active site, and the overall protein structures were left unchanged, although some small but significant side chain movements at the active site were observed. Vanadate ion formed a covalent linkage with the nucleophile Cys12 at the active site and exhibited a trigonal bipyramidal geometry. In contrast, simple tetrahedral geometry was observed for the weaker molybdate complex. These studies are consistent with the conclusion that vanadate inhibits tyrosine phosphatases by acting as a transition state analog. The structure of the vanadate complex may be expected to closely resemble the transition state for reactions catalyzed by protein tyrosine phosphatases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21204787 Y.Zhang, M.Zhang, and Y.Zhang (2011).
Crystal structure of Ssu72, an essential eukaryotic phosphatase specific for the C-terminal domain of RNA polymerase II, in complex with a transition state analogue.
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PDB codes: 3omw 3omx
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Buffer interference with protein dynamics: a case study on human liver fatty acid binding protein.
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Targeting proteins with metal complexes.
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19140798 T.A.Brandão, H.Robinson, S.J.Johnson, and A.C.Hengge (2009).
Impaired acid catalysis by mutation of a protein loop hinge residue in a YopH mutant revealed by crystal structures.
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PDB codes: 3f99 3f9a 3f9b
17989002 H.Dau, A.Grundmeier, P.Loja, and M.Haumann (2008).
On the structure of the manganese complex of photosystem II: extended-range EXAFS data and specific atomic-resolution models for four S-states.
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18220476 H.P.Monteiro, R.J.Arai, and L.R.Travassos (2008).
Protein tyrosine phosphorylation and protein tyrosine nitration in redox signaling.
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18851975 J.G.Zalatan, T.D.Fenn, and D.Herschlag (2008).
Comparative enzymology in the alkaline phosphatase superfamily to determine the catalytic role of an active-site metal ion.
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PDB code: 3dyc
18298793 L.Tabernero, A.R.Aricescu, E.Y.Jones, and S.E.Szedlacsek (2008).
Protein tyrosine phosphatases: structure-function relationships.
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18808119 P.A.Sigala, D.A.Kraut, J.M.Caaveiro, B.Pybus, E.A.Ruben, D.Ringe, G.A.Petsko, and D.Herschlag (2008).
Testing geometrical discrimination within an enzyme active site: constrained hydrogen bonding in the ketosteroid isomerase oxyanion hole.
  J Am Chem Soc, 130, 13696-13708.
PDB codes: 2inx 3cpo
17957392 S.A.Gabel, and R.E.London (2008).
Ternary borate-nucleoside complex stabilization by ribonuclease A demonstrates phosphate mimicry.
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17469803 A.Moulin, J.H.Bell, R.F.Pratt, and D.Ringe (2007).
Inhibition of chymotrypsin by a complex of ortho-vanadate and benzohydroxamic acid: structure of the inert complex and its mechanistic interpretation.
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PDB code: 2p8o
17195266 D.Rauh, and H.Waldmann (2007).
Linking chemistry and biology for the study of protein function.
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17008719 D.Tolkatchev, R.Shaykhutdinov, P.Xu, J.Plamondon, D.C.Watson, N.M.Young, and F.Ni (2006).
Three-dimensional structure and ligand interactions of the low molecular weight protein tyrosine phosphatase from Campylobacter jejuni.
  Protein Sci, 15, 2381-2394.
PDB code: 2gi4
16963640 L.Volpon, C.R.Young, A.Matte, and K.Gehring (2006).
NMR structure of the enzyme GatB of the galactitol-specific phosphoenolpyruvate-dependent phosphotransferase system and its interaction with GatA.
  Protein Sci, 15, 2435-2441.
PDB code: 1tvm
16873118 L.Wang, N.M.Goodey, S.J.Benkovic, and A.Kohen (2006).
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16873128 M.H.Olsson, J.Mavri, and A.Warshel (2006).
Transition state theory can be used in studies of enzyme catalysis: lessons from simulations of tunnelling and dynamical effects in lipoxygenase and other systems.
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16873125 M.J.Sutcliffe, L.Masgrau, A.Roujeinikova, L.O.Johannissen, P.Hothi, J.Basran, K.E.Ranaghan, A.J.Mulholland, D.Leys, and N.S.Scrutton (2006).
Hydrogen tunnelling in enzyme-catalysed H-transfer reactions: flavoprotein and quinoprotein systems.
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16873119 R.K.Allemann, R.M.Evans, L.H.Tey, G.Maglia, J.Pang, R.Rodriguez, P.J.Shrimpton, and R.S.Swanwick (2006).
Protein motions during catalysis by dihydrofolate reductases.
  Philos Trans R Soc Lond B Biol Sci, 361, 1317-1321.  
16873124 S.Hammes-Schiffer, and J.B.Watney (2006).
Hydride transfer catalysed by Escherichia coli and Bacillus subtilis dihydrofolate reductase: coupled motions and distal mutations.
  Philos Trans R Soc Lond B Biol Sci, 361, 1365-1373.  
16195543 C.L.Gustafson, C.V.Stauffacher, K.Hallenga, and R.L.Van Etten (2005).
Solution structure of the low-molecular-weight protein tyrosine phosphatase from Tritrichomonas foetus reveals a flexible phosphate binding loop.
  Protein Sci, 14, 2515-2525.
PDB code: 1p8a
16059970 G.Fimland, L.Johnsen, B.Dalhus, and J.Nissen-Meyer (2005).
Pediocin-like antimicrobial peptides (class IIa bacteriocins) and their immunity proteins: biosynthesis, structure, and mode of action.
  J Pept Sci, 11, 688-696.  
16003807 R.S.Swanwick, A.M.Daines, L.H.Tey, S.L.Flitsch, and R.K.Allemann (2005).
Increased thermal stability of site-selectively glycosylated dihydrofolate reductase.
  Chembiochem, 6, 1338-1340.  
15751352 S.Weber, C.W.Kay, A.Bacher, G.Richter, and R.Bittl (2005).
Probing the N(5)-H bond of the isoalloxazine moiety of flavin radicals by X- and W-band pulsed electron-nuclear double resonance.
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15234974 L.Tao, and A.L.Harris (2004).
Biochemical requirements for inhibition of Connexin26-containing channels by natural and synthetic taurine analogs.
  J Biol Chem, 279, 38544-38554.  
15532034 M.D.Disney, J.L.Childs, and D.H.Turner (2004).
Hoechst 33258 selectively inhibits group I intron self-splicing by affecting RNA folding.
  Chembiochem, 5, 1647-1652.  
14716003 M.Garcia-Viloca, J.Gao, M.Karplus, and D.G.Truhlar (2004).
How enzymes work: analysis by modern rate theory and computer simulations.
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15258141 P.M.Legler, M.Cai, A.Peterkofsky, and G.M.Clore (2004).
Three-dimensional solution structure of the cytoplasmic B domain of the mannitol transporter IImannitol of the Escherichia coli phosphotransferase system.
  J Biol Chem, 279, 39115-39121.
PDB code: 1vkr
12704087 D.A.Kraut, K.S.Carroll, and D.Herschlag (2003).
Challenges in enzyme mechanism and energetics.
  Annu Rev Biochem, 72, 517-571.  
12657060 G.Klein, C.Dartigalongue, and S.Raina (2003).
Phosphorylation-mediated regulation of heat shock response in Escherichia coli.
  Mol Microbiol, 48, 269-285.  
12973020 Y.Hasegawa, J.Hamada, M.Morioka, S.Yano, T.Kawano, Y.Kai, K.Fukunaga, and Y.Ushio (2003).
Neuroprotective effect of postischemic administration of sodium orthovanadate in rats with transient middle cerebral artery occlusion.
  J Cereb Blood Flow Metab, 23, 1040-1051.  
12050018 A.M.Evangelou (2002).
Vanadium in cancer treatment.
  Crit Rev Oncol Hematol, 42, 249-265.  
11980490 H.Deng, R.Callender, Z.Huang, and Z.Y.Zhang (2002).
Is the PTPase-vanadate complex a true transition state analogue?
  Biochemistry, 41, 5865-5872.  
11524683 J.Y.Lee, J.E.Kwak, J.Moon, S.H.Eom, E.C.Liong, J.D.Pedelacq, J.Berendzen, and S.W.Suh (2001).
Crystal structure and functional analysis of the SurE protein identify a novel phosphatase family.
  Nat Struct Biol, 8, 789-794.
PDB codes: 1j9j 1j9k 1j9l
11284047 K.Yoshinari, E.V.Petrotchenko, L.C.Pedersen, and M.Negishi (2001).
Crystal structure-based studies of cytosolic sulfotransferase.
  J Biochem Mol Toxicol, 15, 67-75.  
10889041 J.D.Selengut, and R.L.Levine (2000).
MDP-1: A novel eukaryotic magnesium-dependent phosphatase.
  Biochemistry, 39, 8315-8324.  
10684639 S.Wang, L.Tabernero, M.Zhang, E.Harms, R.L.Van Etten, and C.V.Stauffacher (2000).
Crystal structures of a low-molecular weight protein tyrosine phosphatase from Saccharomyces cerevisiae and its complex with the substrate p-nitrophenyl phosphate.
  Biochemistry, 39, 1903-1914.
PDB codes: 1d1p 1d1q
10585426 B.Zhou, and Z.Y.Zhang (1999).
Mechanism of mitogen-activated protein kinase phosphatase-3 activation by ERK2.
  J Biol Chem, 274, 35526-35534.  
10409830 K.Kolmodin, P.Nordlund, and J.Aqvist (1999).
Mechanism of substrate dephosphorylation in low Mr protein tyrosine phosphatase.
  Proteins, 36, 370-379.  
10052933 M.Zhou, and R.L.Van Etten (1999).
Structural basis of the tight binding of pyridoxal 5'-phosphate to a low molecular weight protein tyrosine phosphatase.
  Biochemistry, 38, 2636-2646.  
9850609 A.Morinville, D.Maysinger, and A.Shaver (1998).
From Vanadis to Atropos: vanadium compounds as pharmacological tools in cell death signalling.
  Trends Pharmacol Sci, 19, 452-460.  
9692990 H.Deng, J.Wang, R.H.Callender, J.C.Grammer, and R.G.Yount (1998).
Raman difference spectroscopic studies of the myosin S1.MgADP.vanadate complex.
  Biochemistry, 37, 10972-10979.  
9693007 J.H.Wang, D.G.Xiao, H.Deng, M.R.Webb, and R.Callender (1998).
Raman difference studies of GDP and GTP binding to c-Harvey ras.
  Biochemistry, 37, 11106-11116.  
9756867 M.Sarmiento, Y.Zhao, S.J.Gordon, and Z.Y.Zhang (1998).
Molecular basis for substrate specificity of protein-tyrosine phosphatase 1B.
  J Biol Chem, 273, 26368-26374.  
9705307 M.Zhang, C.V.Stauffacher, D.Lin, and R.L.Van Etten (1998).
Crystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity.
  J Biol Chem, 273, 21714-21720.
PDB code: 5pnt
9545333 R.Ni, Y.Nishikawa, and B.I.Carr (1998).
Cell growth inhibition by a novel vitamin K is associated with induction of protein tyrosine phosphorylation.
  J Biol Chem, 273, 9906-9911.  
9817026 T.R.Burke, and Z.Y.Zhang (1998).
Protein-tyrosine phosphatases: structure, mechanism, and inhibitor discovery.
  Biopolymers, 47, 225-241.  
9765259 Y.Kakuta, E.V.Petrotchenko, L.C.Pedersen, and M.Negishi (1998).
The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis.
  J Biol Chem, 273, 27325-27330.
PDB code: 1bo6
9323207 C.D.Lima, M.G.Klein, and W.A.Hendrickson (1997).
Structure-based analysis of catalysis and substrate definition in the HIT protein family.
  Science, 278, 286-290.
PDB codes: 1av5 1kpe 1kpf 4fit 5fit 6fit
9305993 P.A.Tishmack, D.Bashford, E.Harms, and R.L.Van Etten (1997).
Use of 1H NMR spectroscopy and computer simulations To analyze histidine pKa changes in a protein tyrosine phosphatase: experimental and theoretical determination of electrostatic properties in a small protein.
  Biochemistry, 36, 11984-11994.  
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.