PMID- 11118200
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20240316
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 19
IP  - 24
DP  - 2000 Dec 15
TI  - The structural basis of the catalytic mechanism and regulation of 
      glucose-1-phosphate thymidylyltransferase (RmlA).
PG  - 6652-63
AB  - 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.
FAU - Blankenfeldt, W
AU  - Blankenfeldt W
AD  - The Centre for Biomolecular Sciences, The University, St Andrews, KY16 9ST, UK.
FAU - Asuncion, M
AU  - Asuncion M
FAU - Lam, J S
AU  - Lam JS
FAU - Naismith, J H
AU  - Naismith JH
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Nucleoside Diphosphate Sugars)
RN  - 0 (Protein Subunits)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thymine Nucleotides)
RN  - 2147-59-3 (thymidine diphosphate rhamnose)
RN  - EC 2.7.7.- (Nucleotidyltransferases)
RN  - EC 2.7.7.24 (glucose-1-phosphate thymidylyltransferase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Caenorhabditis elegans
MH  - Catalysis
MH  - Cloning, Molecular
MH  - Crystallography, X-Ray
MH  - Escherichia coli
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nucleoside Diphosphate Sugars/biosynthesis/pharmacology
MH  - Nucleotidyltransferases/*chemistry/*metabolism
MH  - Protein Structure, Secondary
MH  - Protein Subunits
MH  - Pseudomonas aeruginosa/*enzymology
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Thymine Nucleotides/biosynthesis/pharmacology
PMC - PMC305900
EDAT- 2000/12/16 11:00
MHDA- 2001/03/03 10:01
PMCR- 2001/12/15
CRDT- 2000/12/16 11:00
PHST- 2000/12/16 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/12/16 11:00 [entrez]
PHST- 2001/12/15 00:00 [pmc-release]
AID - cdd673 [pii]
AID - 10.1093/emboj/19.24.6652 [doi]
PST - ppublish
SO  - EMBO J. 2000 Dec 15;19(24):6652-63. doi: 10.1093/emboj/19.24.6652.