PDBsum entry: 5pnt

Hydrolase

PDB id: 5pnt

Contents

Protein chain

157 a.a. *

Ligands

MES

Waters ×82

* Residue conservation analysis

PDB id:

5pnt

Name:

Hydrolase

Title:

Crystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity

Structure:

Low molecular weight phosphotyrosyl phosphatase. Chain: a. Synonym: orthophosphoric monoester phosphohydrolase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytosol. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

2.20Å R-factor: 0.181 R-free: 0.248

Authors:

M.Zhang,C.Stauffacher,D.Lin,R.Vanetten

Key ref:

M.Zhang et al. (1998). Crystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity. J Biol Chem, 273, 21714-21720. PubMed id: 9705307 DOI: 10.1074/jbc.273.34.21714

Date:

29-Apr-98 Release date: 14-Oct-98

Protein chain

P24666  (PPAC_HUMAN) -  Low molecular weight phosphotyrosine protein phosphatase

Seq: 158 a.a.

Struc: 157 a.a.

Enzyme reactions

• Enzyme class 2: E.C.3.1.3.2 - Acid phosphatase.
• Reaction: A phosphate monoester + H₂O = an alcohol + phosphate
• Enzyme class 3: E.C.3.1.3.48 - Protein-tyrosine-phosphatase.
• Reaction: Protein tyrosine phosphate + H₂O = 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 

• Cellular component: soluble fraction (2 terms)
• Biological process: protein amino acid dephosphorylation (1 term)
• Biochemical function: hydrolase activity (6 terms)

reference

DOI no: 10.1074/jbc.273.34.21714

J Biol Chem 273:21714-21720 (1998)

PubMed id: 9705307

Crystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity.

M.Zhang, C.V.Stauffacher, D.Lin, R.L.Van Etten.

ABSTRACT

The low molecular weight phosphotyrosine phosphatases (PTPases) constitute a distinctive class of phosphotyrosine phosphatases that is widely distributed among vertebrate and invertebrate organisms. In vertebrates, two isoenzymes of these low molecular weight PTPases are commonly expressed. The two human isoenzymes, HCPTPA and HCPTPB, differ in an alternatively spliced sequence (residues 40-73) referred to as the variable loop, resulting in isoenzymes that have different substrate specificities and inhibitor/activator responses. We present here the x-ray crystallographic structure of a human low molecular weight PTPase solved by molecular replacement to 2.2 A. The structure of human low molecular weight PTPase is compared with a structure representing the other isoenzyme in this PTPase class, in each case with a sulfonate inhibitor bound to the active site. Possible aromatic residue interactions with the phosphotyrosine substrate are proposed from an examination of the binding site of the inhibitors. Differences are observed in the variable loop region, which forms one wall and the floor of a long crevice leading from the active-site loop. A set of residues lying along this crevice (amino acids 49, 50, and 53) is suggested to be responsible for differences in substrate specificity in these two enzymes.

Selected figure(s)

Figure 1.
Fig. 1. Sequence alignment of human (HCPTPA and HCPTPB) and bovine (BPTP) low molecular weight phosphotyrosyl phosphatases (17, 20). Secondary structure elements shown under the sequences represent the structure of the human isoenzyme HCPTPA as established here. HCPTPA is the electrophoretically fast form of the isoenzyme, and HCPTPB is the slow form. BPTP is 94% identical in sequence to the human B (slow form) but only 81% identical to the human A (fast form) (17). Critical catalytic residues are highlighted in black. The universal PTPase consensus sequence CXXXXXR(S/T), which forms the active site P loop, appears in these proteins as the sequence CLGNICRS from residues 12 to 19 (black highlighting). The acidic residue Asp-129, which protonates the tyrosyl leaving group, is also highlighted in black. The variable sequence region that defines the difference between the human isoenzymes lies between residues 40 and 73 (gray highlighting). This figure was created with the program ALSCRIPT (21).

Figure 3.
Fig. 3. 2Fo-Fc electron density for MES and HEPES in the structures of HCPTPA and BPTP. In each case the view shown is perpendicular to the inhibitor ring. Residues immediately surrounding these sulfonate inhibitors are shown, including the Arg-18 of the active-site loop. The density for the inhibitors is contoured at a level corresponding to that of the protein (1.5 ) and indicates that both molecules are well-ordered in the structure.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1998, 273, 21714-21720) copyright 1998.

Figures were selected by an automated process.