2z9i
From Proteopedia
Crystal structure of RV0983 from Mycobacterium tuberculosis- Proteolytically active form
Structural highlights
FunctionPEPD_MYCTU Required for virulence (PubMed:18479146). Acts both as a protease, which degrades and/or refolds damaged substrate targets, and as a chaperone (PubMed:18479146, PubMed:20061478). Plays an important role in the stress response network mediated through the two-component regulatory system MprAB and SigE signaling networks (PubMed:20061478). May utilize its PDZ domain to recognize and process misfolded proteins at the cell membrane, leading to activation of the MprAB and SigE signaling pathways and subsequent establishment of a positive feedback loop that facilitates bacterial adaptation (PubMed:20061478). Interacts with and potentially cleaves several proteins, including the 35 kDa antigen PspA (PubMed:21445360). Proteolytic cleavage of PspA may help to maintain cell envelope homeostasis in Mycobacterium and regulate specific stress response pathways during periods of extracytoplasmic stress (PubMed:21445360). In vitro, exhibits proteolytic activity against the artificial substrate beta-casein (PubMed:18479146, PubMed:20061478).[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe high-temperature requirement A (HtrA) family of serine proteases has been shown to play an important role in the environmental and cellular stress damage control system in Escherichia coli. Mycobacterium tuberculosis ( Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB. Biochemical analysis reveals that HtrA2 can function both as a protease and as a chaperone. The three-dimensional structure of HtrA2 determined at 2.0 A resolution shows that the protease domains form the central core of the trimer and the PDZ domains extend to the periphery. Unlike E. coli DegS and DegP, the protease is naturally active due to the formation of the serine protease-like catalytic triad and its uniquely designed oxyanion hole. Both protease and PDZ binding pockets of each HtrA2 molecule are occupied by autoproteolytic peptide products and reveal clues for a novel autoregulatory mechanism that might have significant importance in HtrA-associated virulence of Mtb. Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis.,Mohamedmohaideen NN, Palaninathan SK, Morin PM, Williams BJ, Braunstein M, Tichy SE, Locker J, Russell DH, Jacobs WR Jr, Sacchettini JC Biochemistry. 2008 Jun 10;47(23):6092-102. Epub 2008 May 15. PMID:18479146[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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