2c90

File:2c90.gif

spinqualitylabelsall models 2c90, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THROMBIN INHIBITORS

OverviewOverview

The screening of fragments is an alternative approach to high-throughput, screening for the identification of leads for therapeutic targets., Fragment hits have been discovered using X-ray crystallographic screening, of protein crystals of the serine protease enzyme thrombin. The fragment, library was designed to avoid any well-precedented, strongly basic, functionality. Screening hits included a novel ligand (3), which binds, exclusively to the S2-S4 pocket, in addition to smaller fragments which, bind to the S1 pocket. The structure of these protein-ligand complexes are, presented. A chemistry strategy to link two such fragments together and to, synthesize larger drug-sized compounds resulted in the efficient, identification of hybrid inhibitors with nanomolar potency (e.g., 7, IC50, = ... [(full description)]

About this StructureAbout this Structure

2C90 is a [Protein complex] structure of sequences from [Hirudo medicinalis] and [Homo sapiens] with NA, DMS and C1M as [ligands]. Active as [Thrombin], with EC number [3.4.21.5]. Structure known Active Site: AC1. Full crystallographic information is available from [OCA].

ReferenceReference

Application of fragment screening and fragment linking to the discovery of novel thrombin inhibitors., Howard N, Abell C, Blakemore W, Chessari G, Congreve M, Howard S, Jhoti H, Murray CW, Seavers LC, van Montfort RL, J Med Chem. 2006 Feb 23;49(4):1346-55. PMID:16480269

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