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PDBsum entry 1a4x
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Transcription regulation
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PDB id
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1a4x
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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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Adaptation of an enzyme to regulatory function: structure of bacillus subtilis pyrr, A pyr RNA-Binding attenuation protein and uracil phosphoribosyltransferase.
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Authors
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D.R.Tomchick,
R.J.Turner,
R.L.Switzer,
J.L.Smith.
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Ref.
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Structure, 1998,
6,
337-350.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The expression of pyrimidine nucleotide biosynthetic (pyr) genes in
Bacillus subtilis is regulated by transcriptional attenuation. The PyrR
attenuation protein binds to specific sites in pyr mRNA, allowing the formation
of downstream terminator structures. UMP and 5-phosphoribosyl-1-pyrophosphate
(PRPP), a nucleotide metabolite, are co-regulators with PyrR. The smallest RNA
shown to bind tightly to PyrR is a 28-30 nucleotide stem-loop that contains a
purine-rich bulge and a putative-GNRA tetraloop. PyrR is also a uracil
phosphoribosyltransferase (UPRTase), although the relationship between enzymatic
activity and RNA recognition is unclear, and the UPRTase activity of PyrR is not
physiologically significant in B. subtilis. Elucidating the role of PyrR
structural motifs in UMP-dependent RNA binding is an important step towards
understanding the mechanism of pyr transcriptional attenuation. RESULTS: The 1.6
A crystal structure of B. subtilis PyrR has been determined by multiwavelength
anomalous diffraction, using a Sm co-crystal. As expected, the structure of PyrR
is homologous to those proteins of the large type I PRTase structural family; it
is most similar to hypoxanthine-guanine-xanthine PRTase (HGXPRTase). The PyrR
dimer differs from other PRTase dimers, suggesting it may have evolved
specifically for RNA binding. A large, basic, surface at the dimer interface is
an obvious RNA-binding site and uracil specificity is probably provided by
hydrogen bonds from mainchain and sidechain atoms in the hood subdomain. These
models of RNA and UMP binding are consistent with biological data. CONCLUSIONS:
The B. subtilis protein PyrR has adapted the substrate- and product-binding
capacities of a PRTase, probably an HGXPRTase, producing a new regulatory
function in which the substrate and product are co-regulators of transcription
termination. The structure is consistent with the idea that PyrR regulatory
function is independent of catalytic activity, which is likely to be extremely
low under physiological conditions.
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Figure 6.
Figure 6. Stereo view of a model of UMP bound to the active
site of the PyrR monomer from the dimer crystal structure.
Protein residues implicated in catalytic activity and/or UMP
coordination are shown with black bonds; UMP is shown with white
bonds; carbon atoms are white; oxygen, nitrogen and phosphorus
are shaded. Potential hydrogen bonds between the UMP base and
protein are shown as dashed lines. One of these hydrogen bonds
is to invariant Arg138 in the dimer loop. The figure was
prepared with the program MOLSCRIPT [71].
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
337-350)
copyright 1998.
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