PDBsum entry 1sug

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Hydrolase PDB id
Protein chain
298 a.a. *
GOL ×4
Waters ×251
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: 1.95 a structure of apo protein tyrosine phosphatase 1b
Structure: Protein-tyrosine phosphatase, non-receptor type 1 chain: a. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn1, ptp1b. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.95Å     R-factor:   0.188     R-free:   0.203
Authors: A.K.Pedersen,G.H.Peters,K.B.Moller,L.F.Iversen,J.S.Kastrup
Key ref:
A.K.Pedersen et al. (2004). Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B. Acta Crystallogr D Biol Crystallogr, 60, 1527-1534. PubMed id: 15333922 DOI: 10.1107/S0907444904015094
26-Mar-04     Release date:   07-Sep-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1
435 a.a.
298 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

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


DOI no: 10.1107/S0907444904015094 Acta Crystallogr D Biol Crystallogr 60:1527-1534 (2004)
PubMed id: 15333922  
Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B.
A.K.Pedersen, G.H.Peters G, K.B.Møller, L.F.Iversen, J.S.Kastrup.
Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator of insulin and leptin signalling and is therefore considered to be an important molecular target for the treatment of type 2 diabetes and obesity. Detailed structural information about the structure of PTP1B, including the conformation and flexibility of active-site residues as well as the water-molecule network, is a key issue in understanding ligand binding and enzyme kinetics and in structure-based drug design. A 1.95 A apo PTP1B structure has been obtained, showing four highly coordinated water molecules in the active-site pocket of the enzyme; hence, the active site is highly solvated in the apo state. Three of the water molecules are located at positions that approximately correspond to the positions of the phosphate O atoms of the natural substrate phosphotyrosine and form a similar network of hydrogen bonds. The active-site WPD-loop was found to be in the closed conformation, in contrast to previous observations of wild-type PTPs in the apo state, in which the WPD-loop is open. The closed conformation is stabilized by a network of hydrogen bonds. These results provide new insights into and understanding of the active site of PTP1B and form a novel basis for structure-based inhibitor design.
  Selected figure(s)  
Figure 2.
Figure 2 Flexibility of apo PTP1B. (a) B values (arbitrarily divided by a factor of 20 and shown as a continuous line) and average value of the r.m.s.d. (shown as columns) extracted from the molecular-dynamics simulations for C^ [156][alpha] atoms as a function of apo PTP1B residue number. The r.m.s.d. data are calculated with respect to the structure extracted after 1 ns simulation. (b) WPD-loop 2F[o] - F[c] omit electron density for the closed and open conformations of the loop is shown in magenta in the upper and lower part of the figure, respectively. All atoms of the WPD-loop are shown in ball-and-stick representation in light green for the closed conformation and in dark green for the open conformation. N atoms are shown in blue and O atoms in red. The figure was prepared using the programs MOLSCRIPT (Kraulis, 1991[157] [Kraulis, P. J. (1991). J. Appl. Cryst. 24, 946-950.]-[158][bluearr.gif] ) and RASTER3D (Merritt & Bacon, 1997[159] [Merritt, E. A. & Bacon, D. J. (1997). Methods Enzymol. 277, 505-524.]-[160][bluearr.gif] ).
  The above figure is reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2004, 60, 1527-1534) copyright 2004.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.
  J Am Chem Soc, 131, 778-786.
PDB codes: 3f99 3f9a 3f9b
18366016 D.Katagiri, H.Fuji, S.Neya, and T.Hoshino (2008).
Ab initio protein structure prediction with force field parameters derived from water-phase quantum chemical calculation.
  J Comput Chem, 29, 1930-1944.  
16916797 P.J.Ala, L.Gonneville, M.C.Hillman, M.Becker-Pasha, M.Wei, B.G.Reid, R.Klabe, E.W.Yue, B.Wayland, B.Douty, P.Polam, Z.Wasserman, M.Bower, A.P.Combs, T.C.Burn, G.F.Hollis, and R.Wynn (2006).
Structural basis for inhibition of protein-tyrosine phosphatase 1B by isothiazolidinone heterocyclic phosphonate mimetics.
  J Biol Chem, 281, 32784-32795.
PDB codes: 2cm2 2cm3 2cm7 2cm8 2cma 2cmb 2cmc
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