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: 2024-04-03) |
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 Cited by 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: 15506754DOI: 10.1021/ja044742u PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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