PDBsum entry 1f5d

Hydrolase

PDB id: 1f5d

Contents

Protein chains

178 a.a.

11 a.a.

Waters ×66

Superseded by:

1j4x

PDB id:

1f5d

Name:

Hydrolase

Title:

Human vh1-related dual-specificity phosphatase c124s mutant- peptide complex

Structure:

Dual specificity protein phosphatase 3. Chain: a. Engineered: yes. Mutation: yes. Protein (11-mer). Chain: d. Engineered: yes

Source:

Homo sapiens. Human. Expressed in: escherichia coli. Synthetic: yes

Resolution:

2.75Å R-factor: 0.192 R-free: 0.260

Authors:

M.A.Schumacher,J.L.Todd,K.G.Tanner,J.M.Denu

Key ref:

C.Sich et al. (2000). Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics. Eur J Biochem, 267, 5342-5355. PubMed id: 10951192 DOI: 10.1046/j.1432-1327.2000.01551.x

Date:

13-Jun-00 Release date: 13-Dec-00

Protein chain

P51452  (DUS3_HUMAN) -  Dual specificity protein phosphatase 3 from Homo sapiens

Seq: 185 a.a.

Struc: 178 a.a.*

Protein chain

No UniProt id for this chain

Struc: 11 a.a.

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

Enzyme reactions

• Enzyme class: Chain A: 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: 10.1046/j.1432-1327.2000.01551.x

Eur J Biochem 267:5342-5355 (2000)

PubMed id: 10951192

Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics.

C.Sich, S.Improta, D.J.Cowley, C.Guenet, J.P.Merly, M.Teufel, V.Saudek.

ABSTRACT

The structure of a recently reported neurotrophic ligand, 3-(3-pyridyl)-1-propyl(2S)-1-(3,3-dimethyl-1, 2-dioxopentyl)-2-pyrrolidinecarboxylate, in complex with FKBP12 was determined using heteronuclear NMR spectroscopy. The inhibitor exhibits a binding mode analogous to that observed for the macrocycle FK506, used widely as an immunosuppressant, with the prolyl ring replacing the pipecolyl moiety and the amide bond in a trans conformation. However, fewer favourable protein-ligand interactions are detected in the structure of the complex, suggesting weaker binding compared with the immunosuppressant drug. Indeed, a micromolar dissociation constant was estimated from the NMR ligand titration profile, in contrast to the previously published nanomolar inhibition activity. Although the inhibitor possesses a remarkable structural simplicity with respect to FK506, 15N relaxation studies show that it induces similar effects on the protein dynamics, stabilizing the conformation of solvent-exposed residues which are important for mediating the interaction of immunophilin/ligand complexes with molecular targets and potentially for the transmission of the neurotrophic action of FKBP12 inhibitors.

Selected figure(s)

Figure 1.
Fig. 1. Chemical structure of the FKBP12 ligand under investigation (1), FK506 and a compound investigated by Holt et al. (2) [1].

Figure 8.
Fig. 8. Stereoview of stick models of 10 of the lowest energy structures of 1 bound to FKBP12. Ligand atoms are colored according to the atom type. The protein is represented by its contact surface.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2000, 267, 5342-5355) copyright 2000.

Figures were selected by an automated process.