4htc
From Proteopedia
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| - | [[Image:4htc.jpg|left|200px]] | + | [[Image:4htc.jpg|left|200px]] |
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| - | '''THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX''' | + | {{Structure |
| + | |PDB= 4htc |SIZE=350|CAPTION= <scene name='initialview01'>4htc</scene>, resolution 2.3Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 4HTC is a [ | + | 4HTC is a [[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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTC OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/1920434 1920434] |
[[Category: Hirudo medicinalis]] | [[Category: Hirudo medicinalis]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: hydrolase(serine protease)]] | [[Category: hydrolase(serine protease)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:09:59 2008'' |
Revision as of 17:10, 20 March 2008
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| , resolution 2.3Å | |||||||
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| Ligands: | |||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Thu Mar 20 19:09:59 2008
