1o75: Difference between revisions

Syphilis is a complex sexually transmitted disease caused by the, spirochetal bacterium Treponema pallidum. T. pallidum has remained, exquisitely sensitive to penicillin, but the mode of action and lethal, targets for beta-lactams are still unknown. We previously identified the, T. pallidum 47-kDa lipoprotein (Tp47) as a penicillin-binding protein, (PBP). Tp47 contains three hypothetical consensus motifs (SVTK, TEN, and, KTG) that typically form the active center of other PBPs. Yet, in this, study, mutations of key amino acids within these motifs failed to abolish, the penicillin binding activity of Tp47. The crystal structure of Tp47 at, a resolution of 1.95 A revealed a fold different from any other known PBP;, Tp47 is predominantly beta-sheet, in contrast to the alpha/beta-fold, common to other PBPs. It comprises four distinct domains: two complex, beta-sheet-containing N-terminal domains and two C-terminal domains that, adopt immunoglobulin-like folds. The three hypothetical PBP signature, motifs do not come together to form a typical PBP active site., Furthermore, Tp47 is unusual in that it displays beta-lactamase activity, (k(cat) for penicillin = 271 +/- 6 s(-1)), a feature that hindered, attempts to identify the active site in Tp47 by co-crystallization and, mass spectrometric techniques. Taken together, Tp47 does not fit the, classical structural and mechanistic paradigms for PBPs, and thus Tp47, appears to represent a new class of PBP.

1O75 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Treponema_pallidum Treponema pallidum] with XE and PDX as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1O75 OCA].  

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