PDBsum entry 1jed

Transferase

PDB id: 1jed

Contents

Protein chains

510 a.a. *

Ligands

ADP ×2

TRS ×2

ACY ×15

Metals

_CD ×11

_CA ×6

_NA ×12

_MG ×4

Waters ×564

* Residue conservation analysis

References listed in PDB file

Key reference

Title

The complex structures of ATP sulfurylase with thiosulfate, Adp and chlorate reveal new insights in inhibitory effects and the catalytic cycle.

Authors

T.C.Ullrich, R.Huber.

Ref.

J Mol Biol, 2001, 313, 1117-1125. [DOI no: 10.1006/jmbi.2001.5098]

PubMed id

11700067

Abstract

The ubiquitous enzyme ATP sulfurylase (ATPS) catalyzes the primary step of intracellular sulfate activation, the formation of adenosine 5'-phosphosulfate (APS). It has been shown that the enzyme catalyzes the generation of APS from ATP and inorganic sulfate in vitro and in vivo, and that this reaction can be inhibited by a number of simple molecules. Here, we present the crystal structures of ATPS from the yeast Saccharomyces cerevisiae complexed with compounds that have inhibitory effects on the catalytic reaction of ATPS. Thiosulfate and ADP mimic the substrates sulfate and ATP in the active site, but are non-reactive and thus competitive inhibitors of the sulfurylase reaction. Chlorate is bound in a crevice between the active site and the intermediate domain III of the complex structure. It forms hydrogen bonds to residues of both domains and stabilizes a "closed" conformation, inhibiting the release of the reaction products APS and PPi. These new observations are evidence for the crucial role of the displacement mechanism for the catalysis by ATPS.

Figure 1.
Figure 1. Stereo view of the thiosulfate complex structure of ATPS, showing the active site in standard orientation. The final 2F[o] -F[c] electron density map at 2.5 Å around the thiosulfate molecule, the cadmium ion and surrounding water molecules is contoured at 1.0s.

Figure 2.
Figure 2. Electrostatic surface potential plot of the ATPS protomer (positive, blue; negative, red), showing (a) the active site of the apo enzyme liganded with a sulfate molecule in its binding pocket. The active site displays an open conformation with the empty pocket for the adenosyl moiety of the nucleotide on the left-hand of the sulfate group. (b) The ADP inhibitor complex shows the active site in a closed conformation after substrate recognition and rigid body displacement with the envelope-like lid shielding the adenosyl moiety of ADP. The putative magnesium ion is coloured in green. (c) Stereo plot of the ADP complex structure of ATPS with the active site in standard orientation. The final 2F[o] -F[c] electron density map at 2.95 Å around ADP and liganding water molecules is contoured at 1.0s. The green density at the phosphate groups of ADP was interpreted and built as a magnesium ion (grey).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 313, 1117-1125) copyright 2001.