1G1L: The Structural Basis of the Catalytic Mechanism and Regulation of Glucose-1-phosphate Thymidylyltransferase (Rmla). Tdp-glucose Complex

The synthesis of deoxy-thymidine di-phosphate (dTDP)-L-rhamnose, an important component of the cell wall of many microorganisms, is a target for therapeutic intervention. The first enzyme in the dTDP-L-rhamnose biosynthetic pathway is glucose-1-phosphate thymidylyltransferase (RmlA). RmlA is inhibited by dTDP-L-rhamnose thereby regulating L-rhamnose production in bacteria. The structure of Pseudomonas aeruginosa RmlA has been solved to 1.66 A resolution. RmlA is a homotetramer, with the monomer consisting of three functional subdomains. The sugar binding and dimerization subdomains are unique to RmlA-like enzymes. The sequence of the core subdomain is found not only in sugar nucleotidyltransferases but also in other nucleotidyltransferases. The structures of five distinct enzyme substrate- product complexes reveal the enzyme mechanism that involves precise positioning of the nucleophile and activation of the electrophile. All the key residues are within the core subdomain, suggesting that the basic mechanism is found in many nucleotidyltransferases. The dTDP-L-rhamnose complex identifies how the protein is controlled by its natural inhibitor. This work provides a platform for the design of novel drugs against pathogenic bacteria.
PDB ID: 1G1LDownload
MMDB ID: 14978
PDB Deposition Date: 2000/10/12
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.77  Å
Source Organism:
Similar Structures:
Biological Unit for 1G1L: tetrameric; determined by author and by software (PISA)
Molecular Components in 1G1L
Label Count Molecule
Proteins (4 molecules)
Glucose-1-phosphate Thymidylyltransferase
Molecule annotation
Chemicals (22 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB