1k22: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1k22.jpg|left|200px]] | [[Image:1k22.jpg|left|200px]] | ||
'''HUMAN THROMBIN-INHIBITOR COMPLEX''' | {{Structure | ||
|PDB= 1k22 |SIZE=350|CAPTION= <scene name='initialview01'>1k22</scene>, resolution 1.93Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=MEL:[((1R)-2-{(2S)-2-[({4-[AMINO(IMINO)METHYL]BENZYL}AMINO)CARBONYL]AZETIDINYL}-1-CYCLOHEXYL-2-OXOETHYL)AMINO]ACETIC ACID'>MEL</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= | |||
}} | |||
'''HUMAN THROMBIN-INHIBITOR COMPLEX''' | |||
==Overview== | ==Overview== | ||
| Line 10: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
1K22 is a [ | 1K22 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=1K22 OCA]. | ||
==Reference== | ==Reference== | ||
Factorising ligand affinity: a combined thermodynamic and crystallographic study of trypsin and thrombin inhibition., Dullweber F, Stubbs MT, Musil D, Sturzebecher J, Klebe G, J Mol Biol. 2001 Oct 26;313(3):593-614. PMID:[http:// | Factorising ligand affinity: a combined thermodynamic and crystallographic study of trypsin and thrombin inhibition., Dullweber F, Stubbs MT, Musil D, Sturzebecher J, Klebe G, J Mol Biol. 2001 Oct 26;313(3):593-614. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11676542 11676542] | ||
[[Category: Hirudo medicinalis]] | [[Category: Hirudo medicinalis]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| Line 24: | Line 33: | ||
[[Category: complex (serine protease/inhibitor)]] | [[Category: complex (serine protease/inhibitor)]] | ||
''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 12:11:28 2008'' | ||
Revision as of 13:11, 20 March 2008
| |||||||
| , resolution 1.93Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN THROMBIN-INHIBITOR COMPLEX
OverviewOverview
The binding of a series of low molecular weight ligands towards trypsin and thrombin has been studied by isothermal titration calorimetry and protein crystallography. In a series of congeneric ligands, surprising changes of protonation states occur and are overlaid on the binding process. They result from induced pK(a) shifts depending on the local environment experienced by the ligand and protein functional groups in the complex (induced dielectric fit). They involve additional heat effects that must be corrected before any conclusion on the binding enthalpy (DeltaH) and entropy (DeltaS) can be drawn. After correction, trends in both contributions can be interpreted in structural terms with respect to the hydrogen bond inventory or residual ligand motions. For all inhibitors studied, a strong negative heat capacity change (DeltaC(p)) is detected, thus binding becomes more exothermic and entropically less favourable with increasing temperature. Due to a mutual compensation, Gibbs free energy remains virtually unchanged. The strong negative DeltaC(p) value cannot solely be explained by the removal of hydrophobic surface portions of the protein or ligand from water exposure. Additional contributions must be considered, presumably arising from modulations of the local water structure, changes in vibrational modes or other ordering parameters. For thrombin, smaller negative DeltaC(p) values are observed for ligand binding in the presence of sodium ions compared to the other alkali ions, probably due to stabilising effects on the protein or changes in the bound water structure.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1K22 is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Factorising ligand affinity: a combined thermodynamic and crystallographic study of trypsin and thrombin inhibition., Dullweber F, Stubbs MT, Musil D, Sturzebecher J, Klebe G, J Mol Biol. 2001 Oct 26;313(3):593-614. PMID:11676542
Page seeded by OCA on Thu Mar 20 12:11:28 2008