PDBsum entry 1y5h

Unknown function

PDB id: 1y5h

Contents

Protein chains

123 a.a. *

Waters ×136

* Residue conservation analysis

PDB id:

1y5h

Name:

Unknown function

Title:

Crystal structure of truncated se-met hypoxic response protein i (hrpi)

Structure:

Hypothetical protein rv2626c. Chain: a, b. Fragment: residues 1-127. Synonym: hypoxic response protein i. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: rv2626c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.50Å R-factor: 0.222 R-free: 0.233

Authors:

M.L.Sharpe,E.N.Baker,J.S.Lott

Key ref:

M.L.Sharpe et al. (2008). The structure and unusual protein chemistry of hypoxic response protein 1, a latency antigen and highly expressed member of the DosR regulon in Mycobacterium tuberculosis. J Mol Biol, 383, 822-836. PubMed id: 18640126 DOI: 10.1016/j.jmb.2008.07.001

Date:

02-Dec-04 Release date: 15-Nov-05

Protein chains

P9WJA3  (HRP1_MYCTU) -  Hypoxic response protein 1 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 143 a.a.

Struc: 123 a.a.

DOI no: 10.1016/j.jmb.2008.07.001

J Mol Biol 383:822-836 (2008)

PubMed id: 18640126

The structure and unusual protein chemistry of hypoxic response protein 1, a latency antigen and highly expressed member of the DosR regulon in Mycobacterium tuberculosis.

M.L.Sharpe, C.Gao, S.L.Kendall, E.N.Baker, J.S.Lott.

ABSTRACT

Mycobacterium tuberculosis adapts to cellular stresses such as decreased oxygen concentration, at least in part, by upregulation of the dormancy survival regulon, which is thought to be important for the bacterium's ability to enter a persistent state in its human host. We have determined the structure of hypoxic response protein 1, a protein encoded by one of the most strongly upregulated genes in the dormancy survival regulon. Hypoxic response protein 1 is an example of a 'cystathionine-beta-synthase-domain-only' protein; however, unlike other cystathionine-beta-synthase domains, it does not appear to bind AMP. The protein is proteolytically sensitive at its C-terminus and contains two unexpected disulfide bonds, one of which appears resistant to reducing agents in solution and is, therefore, most likely buried in the protein and is not solvent-accessible. We show that the protein is secreted from the bacterium in hypoxic in vitro culture and does not accumulate in the bacterial cell wall. The biological function of the protein remains unclear, but we suggest that it may contribute to the modulation of the host immune response. The work reported advances our understanding of the chemistry and cell biology of this intriguing and potentially important protein, and establishes a structural framework for future functional and immunological studies.

Selected figure(s)

Figure 4.
Fig. 4. Variation in the dimerization interfaces of CBS-only proteins. Ribbon diagrams of (a) HRP1, colored as in Fig. 3a, illustrating that contacts between the CBS1 domains dominate the dimerization interface. (b) CBS-only protein YkuL from B. subtilis (PDB ID 1YAV) in green, which shows contributions from both CBS domains to the dimer interface. (c) CBS-only protein TM0892 from Thermot. maritima (PDB ID 1VR9) in cyan, in which the dimerization is mediated by the CBS2 domains. (d) CBS-only protein TA0289 from Thermop. acidophilum^36 (PDB ID 1PVM) in magenta, where the dimer interface is composed of the CBS1 domains and additional C-terminal helices.

Figure 5.
Fig. 5. Rv2626c and AMPKγ CBS domains show conservation around the latter's AMP binding site. The important ligand-interacting side chains in the AMPKγ nonexchangeable AMP binding site, as identified by Xiao et al.,^26 are shown along with their structural equivalents in HRP1. AMPKγ (PDB ID 2V8Q) is shown and labeled in blue; HRP1 is shown in pink and labeled in red.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 383, 822-836) copyright 2008.

Figures were selected by an automated process.