PDBsum entry 1lar

Hydrolase

PDB id: 1lar

Contents

Protein chains

566 a.a. *

533 a.a. *

Waters ×473

* Residue conservation analysis

PDB id:

1lar

Name:

Hydrolase

Title:

Crystal structure of the tandem phosphatase domains of rptp lar

Structure:

Protein (lar). Chain: a, b. Fragment: phosphatase. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: de3

Resolution:

2.00Å R-factor: 0.222 R-free: 0.274

Authors:

H.-J.Nam,F.Poy,N.Krueger,H.Saito,C.A.Frederick

Key ref:

H.J.Nam et al. (1999). Crystal structure of the tandem phosphatase domains of RPTP LAR. Cell, 97, 449-457. PubMed id: 10338209 DOI: 10.1016/S0092-8674(00)80755-2

Date:

20-Apr-99 Release date: 25-Apr-00

Protein chain

P10586  (PTPRF_HUMAN) -  Receptor-type tyrosine-protein phosphatase F from Homo sapiens

Seq: 1907 a.a.

Struc: 566 a.a.*

Protein chain

P10586  (PTPRF_HUMAN) -  Receptor-type tyrosine-protein phosphatase F from Homo sapiens

Seq: 1907 a.a.

Struc: 533 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1016/S0092-8674(00)80755-2

Cell 97:449-457 (1999)

PubMed id: 10338209

Crystal structure of the tandem phosphatase domains of RPTP LAR.

H.J.Nam, F.Poy, N.X.Krueger, H.Saito, C.A.Frederick.

ABSTRACT

Most receptor-like protein tyrosine phosphatases (RPTPs) contain two conserved phosphatase domains (D1 and D2) in their intracellular region. The carboxy-terminal D2 domain has little or no catalytic activity. The crystal structure of the tandem D1 and D2 domains of the human RPTP LAR revealed that the tertiary structures of the LAR D1 and D2 domains are very similar to each other, with the exception of conformational differences at two amino acid positions in the D2 domain. Site-directed mutational changes at these positions (Leu-1644-to-Tyr and Glu-1779-to-Asp) conferred a robust PTPase activity to the D2 domain. The catalytic sites of both domains are accessible, in contrast to the dimeric blocked orientation model previously suggested. The relative orientation of the LAR D1 and D2 domains, constrained by a short linker, is stabilized by extensive interdomain interactions, suggesting that this orientation might be favored in solution.

Selected figure(s)

Figure 1.
Figure 1. Ribbon Diagrams of Two Views of the LAR D1D2 MoleculeD1 and D2 domains are shown in pink and cyan, respectively. On the left, the active site of D1 is facing the viewer and that of D2 is facing upward. On the right, the same molecule is rotated along the horizontal axis approximately 90°. (The relative positions of the two active sites approach a 4-fold screw rotation.) Side chains of residues at the active sites are shown. The loops connecting β1 and β2 of D2 are shown in magenta to indicate the location for the acidic 19-residue insertion in CD45. The boxed region is the interface between the D1 and D2 domains; a detailed view of this area is shown in Figure 5B. The figure was produced using the program SETOR ( [7]).

Figure 3.
Figure 3. Comparisons between the LAR D1 and D2 Domains(A) A superposition of main-chain atoms of the LAR D1 (pink) and D2 (cyan) domains. Disordered residues 1624–1627 of D2 are shown in blue. The loop between the two N-terminal helices (α1′ and α2′) of D2 is marked with an arrow. The side chains of the active site Cys are shown in yellow.(B) A stereo view of the superimposed active sites of the D1 and D2 domains. Side chains of residues involved in catalysis are shown in pink (D1) and cyan (D2). For emphasis, key residues used for comparison between D1 and D2 are colored individually.(C) Surface representation of the active sites of D1 (left) and D2 (right). Residues involved in catalysis are shown in the color scheme following that of the side chains in (B).

The above figures are reprinted by permission from Cell Press: Cell (1999, 97, 449-457) copyright 1999.

Figures were selected by an automated process.