4htc
From Proteopedia
(New page: 200px<br /> <applet load="4htc" size="450" color="white" frame="true" align="right" spinBox="true" caption="4htc, resolution 2.3Å" /> '''THE REFINED STRUCTUR...) |
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caption="4htc, resolution 2.3Å" /> | caption="4htc, resolution 2.3Å" /> | ||
'''THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX'''<br /> | '''THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 4HTC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http:// | + | 4HTC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: hydrolase(serine protease)]] | [[Category: hydrolase(serine protease)]] | ||
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Revision as of 15:45, 15 February 2008
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THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX
Contents |
Overview
The structure of a recombinant hirudin (variant 2, Lys47) human, alpha-thrombin complex has been refined using restrained least-squares, methods to a crystallographic R-factor of 0.173. The hirudin structure, consists of an N-terminal domain folded into a globular unit and a long, 17-peptide C-terminal in an extended chain conformation. The N-terminal, domain binds at the active-site of thrombin where Ile1' to Tyr3', penetrates to the catalytic triad. The alpha-amino group of Ile1' of, hirudin makes a hydrogen bond with OG of Ser195 of thrombin, the, side-chains of Ile1' and Tyr3' occupy the apolar site, Thr2' is at the, entrance to, but does not enter, the S1 specificity site and Ile1' to, Tyr3' form a parallel beta-strand with Ser214 to Gly219. The latter, interaction is antiparallel in all other serine proteinase-protein, inhibitor complexes. The extended C-terminal segment of hirudin, which is, abundant in acidic residues, makes many electrostatic interactions with, the fibrinogen binding exosite while the last five residues are in a 3(10), helical turn residing in a hydrophobic patch on the thrombin surface. The, precision of the complementarity displayed by these two molecules produces, numerous interactions, which although independently generally weak, together are responsible for the high degree of affinity and specificity., Although hirudin-thrombin and D-Phe-Pro-Arg-chloromethyl ketone-thrombin, differ in conformation in the autolysis loop (Lys145 to Gly150), this is, most likely due to different crystal packing interactions and changes in, circular dichroism between the two are probably due to the inherent, flexibility of the loop. An RGD sequence, which is generally known to be, involved in cell surface receptor interactions, occurs in thrombin and is, associated with a long solvent channel filled with water molecules leading, to the surface from the end of the S1 site. However, the RGD triplet does, not appear to be able to interact in concert in a surface binding mode.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
4HTC is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Refined structure of the hirudin-thrombin complex., Rydel TJ, Tulinsky A, Bode W, Huber R, J Mol Biol. 1991 Sep 20;221(2):583-601. PMID:1920434
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