1k1i: Difference between revisions

Revision as of 22:10, 2 May 2008

BOVINE TRYPSIN-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.

About this StructureAbout this Structure

1K1I is a Single protein structure of sequence from Bos taurus. 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 Fri May 2 22:10:57 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1k1i.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1k1i |SIZE=350|CAPTION= <scene name='initialview01'>1k1i</scene>, resolution 2.20&Aring;
+The line below this paragraph, containing "STRUCTURE_1k1i", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FD1:N-ALPHA-(2-NAPHTHYLSULFONYL)-N-(3-AMIDINO-L-PHENYLALANINYL)-D-PIPECOLINIC+ACID'>FD1</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1k1i|  PDB=1k1i  |  SCENE=  }}
-|RELATEDENTRY=[[1k1j|1K1J]], [[1k1l|1K1L]], [[1k1m|1K1M]], [[1k1n|1K1N]], [[1k1o|1K1O]], [[1k1p|1K1P]], [[1k21|1K21]], [[1k22|1K22]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1k1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k1i OCA], [http://www.ebi.ac.uk/pdbsum/1k1i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1k1i RCSB]</span>
-}}
 '''BOVINE TRYPSIN-INHIBITOR COMPLEX'''
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 [[Category: Trypsin]]
 [[Category: Stubbs, M T.]]
-[[Category: hydrolase,serine protease]]
+[[Category: Hydrolase,serine protease]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 22:10:57 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:41:59 2008''