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PDBsum entry 1g0r
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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The structural basis of the catalytic mechanism and regulation of glucose-1-Phosphate thymidylyltransferase (rmla).
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Authors
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W.Blankenfeldt,
M.Asuncion,
J.S.Lam,
J.H.Naismith.
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Ref.
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EMBO J, 2000,
19,
6652-6663.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 1.
Figure 1 (A) The mechanism of the reaction catalysed by RmlA.
(B) The distinct chemical groups that form the ternary complex
with the protein.
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Figure 2.
Figure 2 (A) Stereo ribbon diagram of the RmlA monomer with
location of secondary structure elements. The different colours
denote the three subdomains. Yellow is the core binding
subdomain, light blue is the sugar-binding subdomain and magenta
the dimerization subdomain. The  character
represents a 3[10] helix, and  and
 have
their normal meaning. Secondary structure was assigned with DSSP
(Kabsch and Sander, 1983). (B) A ribbon representation of the
RmlA tetramer. The monomers are coloured red, monomer A; blue,
monomer B; yellow, monomer A'; and light blue, monomer B'. G-1-P
(black) and dTTP (green) are shown at the active sites in
ball-and-stick format. dTDP–L-rhamnose (magenta) is shown in
the secondary binding sites, again as a ball-and-stick diagram.
(C) Same as (B), rotated by 90° around the y-axis. All
molecular representations are prepared with BOBSCRIPT (Esnouf,
1997) through the GL_RENDER interface (L.Esser and
J.Deisenhofer, unpublished data) and were rendered with
POV-Ray™.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2000,
19,
6652-6663)
copyright 2000.
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Secondary reference #1
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Title
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The purification, Crystallization and preliminary structural characterization of glucose-1-Phosphate thymidylyltransferase (rmla), The first enzyme of the dtdp-L-Rhamnose synthesis pathway from pseudomonas aeruginosa.
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Authors
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W.Blankenfeldt,
M.F.Giraud,
G.Leonard,
R.Rahim,
C.Creuzenet,
J.S.Lam,
J.H.Naismith.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2000,
56,
1501-1504.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1 The reaction catalysed by RmlA.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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Secondary reference #2
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Title
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The nucleotide specificity and feedback control of thymidine diphosphate d-Glucose pyrophosphorylase.
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Authors
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A.Melo,
L.Glaser.
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Ref.
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J Biol Chem, 1965,
240,
398-405.
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PubMed id
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