3FBR

structure of HipA-amppnp-peptide

Summary for 3FBR

• Entry DOI: 10.2210/pdb3fbr/pdb
• Related: 3DNT 3DNU 3DNV 3DNW
• Descriptor: Serine/threonine-protein kinase toxin HipA, peptide of EF-Tu, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: persistence, multidrug tolerance hipa, hipb, dna, transcription
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 2
• Total formula weight: 50366.56

Authors

Schumacher, M.A. (deposition date: 2008-11-19, release date: 2009-02-10, Last modification date: 2023-09-06)

Primary citation

Schumacher, M.A.,Piro, K.M.,Xu, W.,Hansen, S.,Lewis, K.,Brennan, R.G.
Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB.
Science, 323:396-401, 2009

PubMed Abstract: Bacterial multidrug tolerance is largely responsible for the inability of antibiotics to eradicate infections and is caused by a small population of dormant bacteria called persisters. HipA is a critical Escherichia coli persistence factor that is normally neutralized by HipB, a transcription repressor, which also regulates hipBA expression. Here, we report multiple structures of HipA and a HipA-HipB-DNA complex. HipA has a eukaryotic serine/threonine kinase-like fold and can phosphorylate the translation factor EF-Tu, suggesting a persistence mechanism via cell stasis. The HipA-HipB-DNA structure reveals the HipB-operator binding mechanism, approximately 70 degrees DNA bending, and unexpected HipA-DNA contacts. Dimeric HipB interacts with two HipA molecules to inhibit its kinase activity through sequestration and conformational inactivation. Combined, these studies suggest mechanisms for HipA-mediated persistence and its neutralization by HipB.

PubMed: 19150849
DOI: 10.1126/science.1163806

Experimental method

X-RAY DIFFRACTION (3.5 Å)