1ppb
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THE REFINED 1.9 ANGSTROMS CRYSTAL STRUCTURE OF HUMAN ALPHA-THROMBIN: INTERACTION WITH D-PHE-PRO-ARG CHLOROMETHYLKETONE AND SIGNIFICANCE OF THE TYR-PRO-PRO-TRP INSERTION SEGMENT
OverviewOverview
A stoichiometric complex formed between human alpha-thrombin and, D-Phe-Pro-Arg chloromethylketone was crystallized in an orthorhombic, crystal form. Orientation and position of a starting model derived from, homologous modelling were determined by Patterson search methods. The, thrombin model was completed in a cyclic modelling-crystallographic, refinement procedure to a final R-value of 0.171 for X-ray data to 1.92 A., The structure is in full agreement with published cDNA sequence data. The, A-chain, ordered only in its central part, is positioned along the, molecular surface opposite to the active site. The B-chain exhibits the, characteristic polypeptide fold of trypsin-like proteinases. Several, extended insertions form, however, large protuberances; most important for, interaction with macromolecular substrates is the characteristic thrombin, loop around Tyr60A-Pro60B-Pro60C-Trp60D (chymotrypsinogen numbering) and, the enlarged loop around the unique Trp148. The former considerably, restricts the active site cleft and seems likely to be responsible for, poor binding of most natural proteinase inhibitors to thrombin. The, exceptional specificity of D-Phe-Pro-Arg chloromethylketone can be, explained by a hydrophobic cage formed by Ile174, Trp215, Leu99, His57, Tyr60A and Trp60D. The narrow active site cleft, with a more polar base, and hydrophobic rims, extends towards the arginine-rich surface of loop, Lys70-Glu80 that probably represents part of the anionic binding region, for hirudin and fibrinogen.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1PPB is a Protein complex structure of sequences from Homo sapiens with CH2 as ligand. The following page contains interesting information on the relation of 1PPB with [Thrombin]. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment., Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J, EMBO J. 1989 Nov;8(11):3467-75. PMID:2583108
Page seeded by OCA on Mon Nov 12 18:46:00 2007