1rre
Crystal structure of E.coli Lon proteolytic domain
Structural highlights
FunctionLON_ECOLI ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins as well as certain short-lived regulatory proteins, including some antitoxins. Required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress. Degrades polypeptides processively to yield small peptide fragments that are 5 to 10 amino acids long. Binds to DNA in a double-stranded, site-specific manner. Endogenous substrates include the regulatory proteins RcsA and SulA, the transcriptional activator SoxS, and UmuD. Its overproduction specifically inhibits translation through at least two different pathways, one of them being the YoeB-YefM toxin-antitoxin system.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedATP-dependent Lon protease degrades specific short-lived regulatory proteins as well as defective and abnormal proteins in the cell. The crystal structure of the proteolytic domain (P domain) of the Escherichia coli Lon has been solved by single-wavelength anomalous dispersion and refined at 1.75-A resolution. The P domain was obtained by chymotrypsin digestion of the full-length, proteolytically inactive Lon mutant (S679A) or by expression of a recombinant construct encoding only this domain. The P domain has a unique fold and assembles into hexameric rings that likely mimic the oligomerization state of the holoenzyme. The hexamer is dome-shaped, with the six N termini oriented toward the narrower ring surface, which is thus identified as the interface with the ATPase domain in full-length Lon. The catalytic sites lie in a shallow concavity on the wider distal surface of the hexameric ring and are connected to the proximal surface by a narrow axial channel with a diameter of approximately 18 A. Within the active site, the proximity of Lys(722) to the side chain of the mutated Ala(679) and the absence of other potential catalytic side chains establish that Lon employs a Ser(679)-Lys(722) dyad for catalysis. Alignment of the P domain catalytic pocket with those of several Ser-Lys dyad peptide hydrolases provides a model of substrate binding, suggesting that polypeptides are oriented in the Lon active site to allow nucleophilic attack by the serine hydroxyl on the si-face of the peptide bond. The catalytic domain of Escherichia coli Lon protease has a unique fold and a Ser-Lys dyad in the active site.,Botos I, Melnikov EE, Cherry S, Tropea JE, Khalatova AG, Rasulova F, Dauter Z, Maurizi MR, Rotanova TV, Wlodawer A, Gustchina A J Biol Chem. 2004 Feb 27;279(9):8140-8. Epub 2003 Dec 9. PMID:14665623[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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