2iwb

From Proteopedia

Revision as of 17:27, 18 December 2007

MECR1 UNBOUND EXTRACELLULAR ANTIBIOTIC-SENSOR DOMAIN.

Overview

Methicillin-resistant Staphylococcus aureus (MRSA) strains are responsible, for most hospital-onset bacterial infections. Lately, they have become a, major threat to the community through infections of skin, soft tissue and, respiratory tract, and subsequent septicaemia or septic shock. MRSA, strains are resistant to most beta-lactam antibiotics (BLAs) as a result, of the biosynthesis of a penicillin-binding protein with low affinity for, BLAs, called PBP2a, PBP2' or MecA. This response is regulated by the, chromosomal mec-divergon, which encodes a signal-transduction system, including a transcriptional repressor, MecI, and a sensor/transducer, MecR1, as well as the structural mecA gene. This system is similar to, those encoded by bla divergons in S. aureus and Bacillus licheniformis., MecR1 comprises an integral-membrane latent metalloprotease domain facing, the cytosol and an extracellular sensor domain. The latter binds BLAs and, transmits a signal through the membrane that eventually triggers, activation of the metalloprotease moiety, which in turn switches off, MecI-induced repression of mecA transcription. The MecR1 sensor domain, MecR1-PBD, reveals a two-domain structure of alpha/beta-type fold, reminiscent of penicillin-binding proteins and beta-lactamases, and a, catalytic serine residue as the ultimate cause for BLA-binding. Covalent, complexes with benzylpenicillin and oxacillin provide evidence that serine, acylation does not entail significant structural changes, thus supporting, the hypothesis that additional extracellular segments of MecR1 are, involved in signal transmission. The chemical nature of the residues, shaping the active-site cleft favours stabilisation of the acyl enzyme, complexes in MecR1-PBD, in contrast to the closely related OXA, beta-lactamases, where the cleft is more likely to promote subsequent, hydrolysis. The present structural data provide insights into the, mec-encoded BLA-response mechanism and an explanation for kinetic, differences in signal transmission with the related bla-encoded systems.

About this Structure

2IWB is a Single protein structure of sequence from Staphylococcus aureus with NI and GOL as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Unbound and acylated structures of the MecR1 extracellular antibiotic-sensor domain provide insights into the signal-transduction system that triggers methicillin resistance., Marrero A, Mallorqui-Fernandez G, Guevara T, Garcia-Castellanos R, Gomis-Ruth FX, J Mol Biol. 2006 Aug 18;361(3):506-21. Epub 2006 Jul 7. PMID:16846613

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