Structure and mechanism of an ADP-glucose phosphorylase from Arabidopsis thaliana

Biochemistry. 2006 Mar 14;45(10):3154-62. doi: 10.1021/bi052232m.

Abstract

The X-ray crystal structure of the At5g18200.1 protein has been determined to a nominal resolution of 2.30 A. The structure has a histidine triad (HIT)-like fold containing two distinct HIT-like motifs. The sequence of At5g18200.1 indicates a distant family relationship to the Escherichia coli galactose-1-P uridylyltransferase (GalT): the determined structure of the At5g18200.1 protein confirms this relationship. The At5g18200.1 protein does not demonstrate GalT activity but instead catalyzes adenylyl transfer in the reaction of ADP-glucose with various phosphates. The best acceptor among those evaluated is phosphate itself; thus, the At5g18200.1 enzyme appears to be an ADP-glucose phosphorylase. The enzyme catalyzes the exchange of (14)C between ADP-[(14)C]glucose and glucose-1-P in the absence of phosphate. The steady state kinetics of exchange follows the ping-pong bi-bi kinetic mechanism, with a k(cat) of 4.1 s(-)(1) and K(m) values of 1.4 and 83 microM for ADP-[(14)C]glucose and glucose-1-P, respectively, at pH 8.5 and 25 degrees C. The overall reaction of ADP-glucose with phosphate to produce ADP and glucose-1-P follows ping-pong bi-bi steady state kinetics, with a k(cat) of 2.7 s(-)(1) and K(m) values of 6.9 and 90 microM for ADP-glucose and phosphate, respectively, at pH 8.5 and 25 degrees C. The kinetics are consistent with a double-displacement mechanism that involves a covalent adenylyl-enzyme intermediate. The X-ray crystal structure of this intermediate was determined to 1.83 A resolution and shows the AMP group bonded to His(186). The value of K(eq) in the direction of ADP and glucose-1-P formation is 5.0 at pH 7.0 and 25 degrees C in the absence of a divalent metal ion, and it is 40 in the presence of 1 mM MgCl(2).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Diphosphate Glucose / metabolism
  • Amino Acid Sequence
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / metabolism
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Enzyme Activation
  • Escherichia coli
  • Glucose-1-Phosphate Adenylyltransferase / chemistry*
  • Glucose-1-Phosphate Adenylyltransferase / metabolism
  • Humans
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleotidyltransferases / metabolism
  • Phosphates / metabolism
  • Protein Conformation
  • Protein Folding
  • Sequence Alignment
  • Sequence Analysis, Protein
  • Structure-Activity Relationship
  • UDPglucose-Hexose-1-Phosphate Uridylyltransferase / metabolism
  • Zinc / metabolism

Substances

  • Arabidopsis Proteins
  • Phosphates
  • Adenosine Diphosphate Glucose
  • Adenosine Diphosphate
  • Nucleotidyltransferases
  • UDPglucose-Hexose-1-Phosphate Uridylyltransferase
  • ADP-glucose pyrophosphorylase, Arabidopsis
  • Glucose-1-Phosphate Adenylyltransferase
  • glutamine-synthetase adenylyltransferase
  • Zinc

Associated data

  • PDB/1Z84
  • PDB/1ZWJ