1way

File:1way.gif

spinqualitylabelsall models 1way, resolution 2.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

ACTIVE SITE THROMBIN INHIBITORS

OverviewOverview

Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper.

DiseaseDisease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this StructureAbout this Structure

1WAY is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Thrombin, with EC number 3.4.21.5 Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Fragment-based lead discovery using X-ray crystallography., Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H, J Med Chem. 2005 Jan 27;48(2):403-13. PMID:15658854

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