| Autor: |
Harris MS; Structural, Analytical and Medicinal Chemistry, Pharmacia Corporation, 301 Henrietta Street, Kalamazoo, MI 49007, USA. melissa.s.harris@pharmacia.com, Bock JH, Choi G, Cialdella JS, Curry KA, Deibel MR Jr, Jacobsen EJ, Marshall VP, Murray RW Jr, Vosters AF, Wolfe CL, Yem AW, Baldwin ET |
| Jazyk: |
angličtina |
| Zdroj: |
Acta crystallographica. Section D, Biological crystallography [Acta Crystallogr D Biol Crystallogr] 2002 Dec; Vol. 58 (Pt 12), pp. 2153-6. Date of Electronic Publication: 2002 Nov 23. |
| DOI: |
10.1107/s090744490201569x |
| Abstrakt: |
In bacteria the biosynthesis of all nascent polypeptides begins with N-formylmethionine. The post-translational removal of the N-formyl group is carried out by peptide deformylase (PDF). Processing of the N-formyl group from critical bacterial proteins is required for cell survival. This formylation/deformylation cycle is unique to eubacteria and is not utilized in eucaryotic cytosolic protein biosynthesis. Thus, inhibition of PDF would halt bacterial growth, spare host cell-function, and would be a novel mechanism for a new class of antibiotic. Diffraction-quality Se-met crystals of S. aureus PDF were prepared that belong to space group C222(1) with unit cell parameters of a = 94.1 b = 121.9 c = 47.6 A. Multiple anomalous dispersion data were collected at the Advanced Photon Source 17-ID beamline and used to solve the PDF structure to 1.9 A resolution. Crystals were also prepared with three PDF inhibitors: thiorphan, actinonin and PNU-172550. The thiorphan and actinonin co-crystals belong to space group C222(1) with similar unit-cell dimensions. Repeated attempts to generate a complex structure of PDF with PNU-172550 from the orthorhombic space group were unsuccessful. Crystallization screening identified an alternate C2 crystal form with unit-cell dimensions of a = 93.4 b = 42.5 c = 104.1 A, beta = 93 degrees. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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