PDBsum entry 1fj2

Hydrolase

PDB id: 1fj2

Contents

Protein chain

229 a.a. *

Metals

_BR ×40

Waters ×465

* Residue conservation analysis

PDB id:

1fj2

Name:

Hydrolase

Title:

Crystal structure of the human acyl protein thioesterase 1 at 1.5 a resolution

Structure:

Protein (acyl protein thioesterase 1). Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.50Å R-factor: 0.183 R-free: 0.237

Authors:

Y.Devedjiev,Z.Dauter,S.Kuznetsov,T.Jones,Z.Derewenda

Key ref:

Y.Devedjiev et al. (2000). Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A. Structure, 8, 1137-1146. PubMed id: 11080636 DOI: 10.1016/S0969-2126(00)00529-3

Date:

07-Aug-00 Release date: 29-Nov-00

Protein chains

O75608  (LYPA1_HUMAN) -  Acyl-protein thioesterase 1 from Homo sapiens

Seq: 230 a.a.

Struc: 229 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.3.1.2.- - ?????
• Enzyme class 3: E.C.3.1.2.22 - palmitoyl-protein hydrolase.
• Reaction: S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H⁺

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

Key reference

DOI no: 10.1016/S0969-2126(00)00529-3

Structure 8:1137-1146 (2000)

PubMed id: 11080636

Crystal structure of the human acyl protein thioesterase I from a single X-ray data set to 1.5 A.

Y.Devedjiev, Z.Dauter, S.R.Kuznetsov, T.L.Jones, Z.S.Derewenda.

ABSTRACT

BACKGROUND: Many proteins undergo posttranslational modifications involving covalent attachment of lipid groups. Among them is palmitoylation, a dynamic, reversible process that affects trimeric G proteins and Ras and constitutes a regulatory mechanism for signal transduction pathways. Recently, an acylhydrolase previously identified as lysophospholipase has been shown to function as an acyl protein thioesterase, which catalyzes depalmitoylation of Galpha proteins as well as Ras. Its amino acid sequence suggested that the protein is evolutionarily related to neutral lipases and other thioesterases, but direct structural information was not available. RESULTS: We have solved the crystal structure of the human putative Galpha-regulatory protein acyl thioesterase (hAPT1) with a single data set collected from a crystal containing the wild-type protein. The phases were calculated to 1.8 A resolution based on anomalous scattering from Br(-) ions introduced in the cryoprotectant solution in which the crystal was soaked for 20 s. The model was refined against data extending to a resolution of 1.5 A to an R factor of 18.6%. The enzyme is a member of the ubiquitous alpha/beta hydrolase family, which includes other acylhydrolases such as the palmitoyl protein thioesterase (PPT1). CONCLUSIONS: The human APT1 is closely related to a previously described carboxylesterase from Pseudomonas fluorescens. The active site contains a catalytic triad of Ser-114, His-203, and Asp-169. Like carboxylesterase, hAPT1 appears to be dimeric, although the mutual disposition of molecules in the two dimers differs. Unlike carboxylesterase, the substrate binding pocket and the active site of hAPT1 are occluded by the dimer interface, suggesting that the enzyme must dissociate upon interaction with substrate.

Selected figure(s)

Figure 3.
Figure 3. Comparison of the Structures of hAPT1 and CPf(a) Ribbon presentation of the superposition of Ca atoms of carboxyl esterase (blue) onto the structure of hAPT1 (gold). Labeled active site residues are shown by ball and stick models.(b) Difference distance plot of the corresponding Ca atoms

The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1137-1146) copyright 2000.

Figure was selected by an automated process.