4GXO

Crystal structure of Staphylococcus aureus protein SarZ mutant C13E

Summary for 4GXO

• Entry DOI: 10.2210/pdb4gxo/pdb
• Descriptor: MarR family regulatory protein, GLYCEROL (3 entities in total)
• Functional Keywords: transcriptional regulator, transcription, structural genomics
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 33150.04

Authors

Sun, F.,Ding, Y.,Ji, Q.,Liang, Z.,Deng, X.,Wong, C.C.,Yi, C.,Zhang, L.,Xie, S.,Alvarez, S.,Hicks, L.M.,Luo, C.,Jiang, H.,Lan, L.,He, C. (deposition date: 2012-09-04, release date: 2012-09-26, Last modification date: 2024-02-28)

Primary citation

Sun, F.,Ding, Y.,Ji, Q.,Liang, Z.,Deng, X.,Wong, C.C.,Yi, C.,Zhang, L.,Xie, S.,Alvarez, S.,Hicks, L.M.,Luo, C.,Jiang, H.,Lan, L.,He, C.
Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance.
Proc.Natl.Acad.Sci.USA, 109:15461-15466, 2012

PubMed Abstract: Protein posttranslational modifications (PTMs), particularly phosphorylation, dramatically expand the complexity of cellular regulatory networks. Although cysteine (Cys) in various proteins can be subject to multiple PTMs, its phosphorylation was previously considered a rare PTM with almost no regulatory role assigned. We report here that phosphorylation occurs to a reactive cysteine residue conserved in the staphylococcal accessary regulator A (SarA)/MarR family global transcriptional regulator A (MgrA) family of proteins, and is mediated by the eukaryotic-like kinase-phosphatase pair Stk1-Stp1 in Staphylococcus aureus. Cys-phosphorylation is crucial in regulating virulence determinant production and bacterial resistance to vancomycin. Cell wall-targeting antibiotics, such as vancomycin and ceftriaxone, inhibit the kinase activity of Stk1 and lead to decreased Cys-phosphorylation of SarA and MgrA. An in vivo mouse model of infection established that the absence of stp1, which results in elevated protein Cys-phosphorylation, significantly reduces staphylococcal virulence. Our data indicate that Cys-phosphorylation is a unique PTM that can play crucial roles in bacterial signaling and regulation.

PubMed: 22927394
DOI: 10.1073/pnas.1205952109

Experimental method

X-RAY DIFFRACTION (2.05 Å)