2mm3: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==Solution NMR structure of the ternary complex of human ileal bile acid-binding protein with glycocholate and glycochenodeoxycholate== | ||
<StructureSection load='2mm3' size='340' side='right' caption='[[2mm3]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2mm3]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MM3 OCA]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHO:GLYCOCHENODEOXYCHOLIC+ACID'>CHO</scene>, <scene name='pdbligand=GCH:GLYCOCHOLIC+ACID'>GCH</scene><br> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mm3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mm3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mm3 RCSB], [http://www.ebi.ac.uk/pdbsum/2mm3 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human ileal bile acid binding protein (I-BABP) is a member of the family of intracellular lipid-binding proteins and is thought to play a role in the enterohepatic circulation of bile salts. Our group has previously shown that human I-BABP binds two molecules of glycocholate (GCA) with low intrinsic affinity but an extraordinary high degree of positive cooperativity. Besides the strong positive cooperativity, human I-BABP exhibits a high degree of site selectivity in its interactions with GCA and glycochenodeoxycholate (GCDA), the two major bile salts in humans. In this study, on the basis of our first generation nuclear magnetic resonance (NMR) structure of the ternary complex of human I-BABP with GCA and GCDA, we introduced single-residue mutations at certain key positions in the binding pocket that might disrupt a hydrogen-bonding network, a likely way of energetic communication between the two sites. Macroscopic binding parameters were determined using isothermal titration calorimetry, and site selectivity was monitored by NMR spectroscopy of isotopically enriched bile salts. According to our results, cooperativity and site selectivity are not linked in human I-BABP. While cooperativity is governed by a subtle interplay of entropic and enthalpic contributions, site selectivity appears to be determined by more localized enthalpic effects. Possible communication pathways between the two binding sites are discussed. | |||
Determinants of cooperativity and site selectivity in human ileal bile acid binding protein.,Toke O, Monsey JD, DeKoster GT, Tochtrop GP, Tang C, Cistola DP Biochemistry. 2006 Jan 24;45(3):727-37. PMID:16411748<ref>PMID:16411748</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bencsura, A.]] | |||
[[Category: Cistola, D P.]] | |||
[[Category: Covey, D F.]] | |||
[[Category: DeKoster, G T.]] | |||
[[Category: Egyed, O.]] | |||
[[Category: Horvath, G.]] | |||
[[Category: Simon, A.]] | |||
[[Category: Tochtrop, G P.]] | |||
[[Category: Toke, O.]] | |||
[[Category: Enterohepatic circulation]] | |||
[[Category: Lipid binding protein]] | |||
[[Category: Lipid-binding protein]] | |||
[[Category: Orthogonal beta sheet]] | |||
[[Category: Positive binding cooperativity]] | |||
[[Category: Site-selectivity]] | |||
Revision as of 11:12, 7 May 2014
Solution NMR structure of the ternary complex of human ileal bile acid-binding protein with glycocholate and glycochenodeoxycholateSolution NMR structure of the ternary complex of human ileal bile acid-binding protein with glycocholate and glycochenodeoxycholate
Structural highlights
Publication Abstract from PubMedHuman ileal bile acid binding protein (I-BABP) is a member of the family of intracellular lipid-binding proteins and is thought to play a role in the enterohepatic circulation of bile salts. Our group has previously shown that human I-BABP binds two molecules of glycocholate (GCA) with low intrinsic affinity but an extraordinary high degree of positive cooperativity. Besides the strong positive cooperativity, human I-BABP exhibits a high degree of site selectivity in its interactions with GCA and glycochenodeoxycholate (GCDA), the two major bile salts in humans. In this study, on the basis of our first generation nuclear magnetic resonance (NMR) structure of the ternary complex of human I-BABP with GCA and GCDA, we introduced single-residue mutations at certain key positions in the binding pocket that might disrupt a hydrogen-bonding network, a likely way of energetic communication between the two sites. Macroscopic binding parameters were determined using isothermal titration calorimetry, and site selectivity was monitored by NMR spectroscopy of isotopically enriched bile salts. According to our results, cooperativity and site selectivity are not linked in human I-BABP. While cooperativity is governed by a subtle interplay of entropic and enthalpic contributions, site selectivity appears to be determined by more localized enthalpic effects. Possible communication pathways between the two binding sites are discussed. Determinants of cooperativity and site selectivity in human ileal bile acid binding protein.,Toke O, Monsey JD, DeKoster GT, Tochtrop GP, Tang C, Cistola DP Biochemistry. 2006 Jan 24;45(3):727-37. PMID:16411748[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||