1hgt

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spinqualitylabelsall models 1hgt, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF THE HIRUGEN AND HIRULOG 1 COMPLEXES OF ALPHA-THROMBIN

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The isomorphous structures of the hirugen (N-acetylhirudin 53'-64' with, sulfato-Tyr63') and hirulog 1 (D-Phe-Pro-Arg-Pro-(Gly)4, desulfato-Tyr63'-hirugen) complexes of human alpha-thrombin have been, determined and refined at 2.2 A resolution to crystallographic R-factors, of 0.167 and 0.163, respectively. The binding of hirugen to thrombin is, similar to that of the binding of the C-terminal dodecapeptide of hirudin, including that of the terminal 3(10) helical turn. The sulfato Tyr63', which, as a result of sulfation, increases the binding affinity by an, order of magnitude, is involved in an extended hydrogen bonding network, utilizing all three sulfato oxygen atoms. The hirugen-thrombin complex is, the first thrombin structure determined to have an unobstructed active, site; this site is practically identical in positioning of catalytic, residues and in its hydrogen bonding pattern with that of other serine, proteinases. Hirulog 1, which is a poor thrombin substrate, is cleaved at, the Arg3'-Pro4' bond in the crystal structure. The Arg3' of hirulog 1, occupies the specificity site, the D-Phe-Pro-Arg tripeptide is positioned, like that of D-Phe-Pro-Arg chloromethylketone in the active site and the, Pro4'(Gly)4 spacer to hirugen is disordered in the structure, as is the, 3(10) turn of hirugen. The latter must be related to the simultaneous, absence both of sulfation and of the last residue of hirudin (Gln65'). In, addition, the autolysis loop of thrombin (Lys145-Gly150) is disordered in, both structures. Changes in circular dichroism upon hirugen binding are, therefore most likely the result of the flexibility associated with this, loop.

Disease

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

About this Structure

1HGT is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with SO3 as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference

Structure of the hirugen and hirulog 1 complexes of alpha-thrombin., Skrzypczak-Jankun E, Carperos VE, Ravichandran KG, Tulinsky A, Westbrook M, Maraganore JM, J Mol Biol. 1991 Oct 20;221(4):1379-93. PMID:1942057

Page seeded by OCA on Mon Nov 12 17:17:48 2007