1XKZ

Crystal structure of the acylated beta-lactam sensor domain of Blar1 from S. aureus

Summary for 1XKZ

• Entry DOI: 10.2210/pdb1xkz/pdb
• Descriptor: Regulatory protein blaR1, ACYLATED CEFTAZIDIME, SULFATE ION, ... (5 entities in total)
• Functional Keywords: beta-lactam receptor, signal transduction, signaling protein
• Biological source: Staphylococcus aureus
• Cellular location: Cell membrane; Multi-pass membrane protein (Probable): P18357
• Total number of polymer chains: 4
• Total formula weight: 122315.56

Authors

Birck, C.,Cha, J.Y.,Cross, J.,Schulze-Briese, C.,Meroueh, S.O.,Schlegel, H.B.,Mobashery, S.,Samama, J.-P. (deposition date: 2004-09-30, release date: 2004-11-30, Last modification date: 2024-11-13)

Primary citation

Birck, C.,Cha, J.Y.,Cross, J.,Schulze-Briese, C.,Meroueh, S.O.,Schlegel, H.B.,Mobashery, S.,Samama, J.-P.
X-ray crystal structure of the acylated beta-lactam sensor domain of BlaR1 from Staphylococcus aureus and the mechanism of receptor activation for signal transduction
J.Am.Chem.Soc., 126:13945-13947, 2004

PubMed Abstract: Methicillin-resistant strains of Staphylococcus aureus (MRSA) are the major cause of infections worldwide. Transcription of the beta-lactamase and PBP2a resistance genes is mediated by two closely related signal-transducing integral membrane proteins, BlaR1 and MecR1, upon binding of the beta-lactam inducer to the sensor domain. Herein we report the crystal structure at 1.75 A resolution of the sensor domain of BlaR1 in complex with a cephalosporin antibiotic. Activation of the signal transducer involves acylation of serine 389 by the beta-lactam antibiotic, a process promoted by the N-carboxylated side chain of Lys392. We present evidence that, on acylation, the lysine side chain experiences a spontaneous decarboxylation that entraps the sensor in its activated state. Kinetic determinations and quantum mechanical/molecular mechanical calculations and the interaction networks in the crystal structure shed light on how this unprecedented process for activation of a receptor may be achieved and provide insights into the mechanistic features that differentiate the signal-transducing receptor from the structurally related class D beta-lactamases, enzymes of antibiotic resistance.

PubMed: 15506754
DOI: 10.1021/ja044742u

Experimental method

X-RAY DIFFRACTION (1.75 Å)