PDBsum entry 1a4x

Transcription regulation

PDB id: 1a4x

Contents

Protein chains

167 a.a. *

Ligands

SO4 ×2

Waters ×237

* Residue conservation analysis

PDB id:

1a4x

Name:

Transcription regulation

Title:

Pyrr, the bacillus subtilis pyrimidine biosynthetic operon repressor, hexameric form

Structure:

Pyrimidine operon regulatory protein pyrr. Chain: a, b. Synonym: pyrr. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 1423. Gene: pyrr. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.30Å R-factor: 0.211 R-free: 0.247

Authors:

D.R.Tomchick,R.J.Turner,R.W.Switzer,J.L.Smith

Key ref:

D.R.Tomchick et al. (1998). Adaptation of an enzyme to regulatory function: structure of Bacillus subtilis PyrR, a pyr RNA-binding attenuation protein and uracil phosphoribosyltransferase. Structure, 6, 337-350. PubMed id: 9551555 DOI: 10.1016/S0969-2126(98)00036-7

Date:

08-Feb-98 Release date: 05-Aug-98

Protein chains

P39765  (PYRR_BACSU) -  Bifunctional protein PyrR from Bacillus subtilis (strain 168)

Seq: 181 a.a.

Struc: 167 a.a.

Enzyme reactions

• Enzyme class: E.C.2.4.2.9 - uracil phosphoribosyltransferase.
• Reaction: UMP + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + uracil

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(98)00036-7

Structure 6:337-350 (1998)

PubMed id: 9551555

Adaptation of an enzyme to regulatory function: structure of Bacillus subtilis PyrR, a pyr RNA-binding attenuation protein and uracil phosphoribosyltransferase.

D.R.Tomchick, R.J.Turner, R.L.Switzer, J.L.Smith.

ABSTRACT

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.

Selected figure(s)

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].

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 337-350) copyright 1998.

Figure was selected by an automated process.