Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.5
Classification:TRANSFERASE
Release Date:2011-11-30
Deposition Date:2011-11-17
Revision Date:2014-03-05#2014-04-09#2017-11-08
Molecular Weight:78211.32
Macromolecule Type:Protein
Residue Count:690
Atom Site Count:5118
DOI:10.2210/pdb3upb/pdb
Abstract:
Arabinose 5-phosphate (A5P) is the aldopentose version of the ketohexose fructose 6-phosphate (F6P), having identical stereochemistry but lacking atoms corresponding to the 1-carbon and 1-hydroxyl. Despite structural similarity and conservation of the reactive portion of F6P, F6P acts as a substrate whereas A5P is reported to be an inhibitor of transaldolase. To address the lack of A5P reactivity we determined a crystal structure of the Francisella tularensis transaldolase in complex with A5P. This structure reveals that like F6P, A5P forms a covalent Schiff base with active site Lys135. Unlike F6P, A5P binding fails to displace an ordered active site water molecule. Retaining this water necessitates conformational changes at the A5P-protein linkage that possibly hinder reactivity. The findings presented here show the basis of A5P inhibition and suggest an unusual mechanism of competitive, reversible-covalent transaldolase regulation.
Resolution:1.5
Classification:TRANSFERASE
Release Date:2011-11-30
Deposition Date:2011-11-17
Revision Date:2014-03-05#2014-04-09#2017-11-08
Molecular Weight:78211.32
Macromolecule Type:Protein
Residue Count:690
Atom Site Count:5118
DOI:10.2210/pdb3upb/pdb
Abstract:
Arabinose 5-phosphate (A5P) is the aldopentose version of the ketohexose fructose 6-phosphate (F6P), having identical stereochemistry but lacking atoms corresponding to the 1-carbon and 1-hydroxyl. Despite structural similarity and conservation of the reactive portion of F6P, F6P acts as a substrate whereas A5P is reported to be an inhibitor of transaldolase. To address the lack of A5P reactivity we determined a crystal structure of the Francisella tularensis transaldolase in complex with A5P. This structure reveals that like F6P, A5P forms a covalent Schiff base with active site Lys135. Unlike F6P, A5P binding fails to displace an ordered active site water molecule. Retaining this water necessitates conformational changes at the A5P-protein linkage that possibly hinder reactivity. The findings presented here show the basis of A5P inhibition and suggest an unusual mechanism of competitive, reversible-covalent transaldolase regulation.
| Date made available | 2011 |
|---|---|
| Publisher | RCSB-PDB |