PDBsum entry: 1y6x

Hydrolase

PDB id: 1y6x

Contents

Protein chain

87 a.a. *

Waters ×151

* Residue conservation analysis

PDB id:

1y6x

Name:

Hydrolase

Title:

The 1.25 a resolution structure of phosphoribosyl-atp pyrophosphohydrolase from mycobacterium tuberculosis

Structure:

Phosphoribosyl-atp pyrophosphatase. Chain: a. Synonym: pra-ph, pratp-ph, phosphoribosyl-atp pyrophosphohy engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Strain: rv37. Gene: hise. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.25Å R-factor: 0.183 R-free: 0.207

Authors:

F.Javid-Majd,J.C.Sacchettini,Tb Structural Genomics Consorti (Tbsgc)

Key ref:

F.Javid-Majd et al. (2008). The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr, 64, 627-635. PubMed id: 18560150 DOI: 10.1107/S0907444908007105

Date:

07-Dec-04 Release date: 01-Mar-05

Protein chain

P0A5B1  (HIS2_MYCTU) -  Phosphoribosyl-ATP pyrophosphatase

Seq: 93 a.a.

Struc: 87 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.1.31 - Phosphoribosyl-ATP diphosphatase.
• Pathway: Histidine Biosynthesis (early stages)
• Reaction: 1-(5-phosphoribosyl)-ATP + H₂O = 1-(5-phosphoribosyl)-AMP + diphosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: growth (4 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1107/S0907444908007105

Acta Crystallogr D Biol Crystallogr 64:627-635 (2008)

PubMed id: 18560150

The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis.

F.Javid-Majd, D.Yang, T.R.Ioerger, J.C.Sacchettini.

ABSTRACT

Phosphoribosyl-ATP pyrophosphohydrolase is the second enzyme in the histidine-biosynthetic pathway, irreversibly hydrolyzing phosphoribosyl-ATP to phosphoribosyl-AMP and pyrophosphate. It is encoded by the hisE gene, which is present as a separate gene in many bacteria and archaea but is fused to hisI in other bacteria, fungi and plants. Because of its essentiality for growth in vitro, HisE is a potential drug target for tuberculosis. The crystal structures of two native (uncomplexed) forms of HisE from Mycobacterium tuberculosis have been determined to resolutions of 1.25 and 1.79 A. The structure of the apoenzyme reveals that the protein is composed of five alpha-helices with connecting loops and is a member of the alpha-helical nucleoside-triphosphate pyrophosphatase superfamily. The biological unit of the protein is a homodimer, with an active site on each subunit composed of residues exclusively from that subunit. A comparison with the Campylobacter jejuni dUTPase active site allowed the identification of putative metal- and substrate-binding sites in HisE, including four conserved glutamate and glutamine residues in the sequence that are consistent with a motif for pyrophosphohydrolase activity. However, significant differences between family members are observed in the loop region between alpha-helices H1 and H3. The crystal structure of M. tuberculosis HisE provides insights into possible mechanisms of substrate binding and the diversity of the nucleoside-triphosphate pyrophosphatase superfamily.

Selected figure(s)

Figure 3.
Figure 3 Superposition of the backbones of Mtb HisE (PDB code 1w2y ; white), S. solfataricus MazG (1vmg ; red), mouse RS21-C6 MazG homolog (2oig ; green) and T. cruzi dUTPase (1w2y ; yellow; residues 110-229 deleted for clarity). The figure illustrates the high variability of the backbone in the loop region connecting helices H1 and H3 (residues 24-37 in Mtb HisE, including helix H2), in contrast to the good alignment of the central helix pair H3 and H4. Also shown is the 5-methyl-dCTP that was complexed with 2oig , indicating the putative substrate-binding region.

Figure 4.
Figure 4 (a) A superposition of the metal-binding site between Mtb HisE crystal form II (white backbone and side chains) and T. cruzi dUTPase (1w2y ; green backbone, gray side chains) complexed with three Mg^2+ ions (orange spheres) and a dUDP analog (dUpNHp). The HisE residues (white) are labeled E48, E51, E67 and Q70. The corresponding dUTPase residues (gray) are E46, E49, E74 and D77. This figure illustrates the coordination of all three Mg^2+ ions by the side chains in 1w2y (gray), including the central Mg^2+ ion, which is coordinated by all four side chains simultaneously, and coordination of two of the Mg^2+ ions to the two phosphates in the ligand. Furthermore, the side chains in the HisE structure are in approximately the same conformation, although they appear to be bound only to water molecules, since the HisE structure is uncomplexed. (b) Molecular surface showing the putative substrate-binding site (crystal form I). The substrate-binding pocket is slightly opened (owing to rotation of Gln70 away), but still constitutes a cluster of highly conserved negatively charged residues (E48, E51 and E67). (c) Superposition of the EXXE metal-binding motifs from the form I crystal (red) and form II crystal (blue). The ordered molecule (density peak modeled as a water molecule) in crystal form II is shown in the center (blue sphere) to illustrate the coordination to all four side chains. In contrast, in crystal form I Q70 is flipped away and the carboxylate of E51 is rotated differently.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2008, 64, 627-635) copyright 2008.

Figures were selected by an automated process.