2mm3: Difference between revisions

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OCA

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 <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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MM3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><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></td></tr>
-<tr id='resources'><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>
+<tr id='resources'><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://pdbe.org/2mm3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mm3 RCSB], [http://www.ebi.ac.uk/pdbsum/2mm3 PDBsum]</span></td></tr>
 </table>
 == Function ==
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 <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.
+Human ileal bile acid binding protein (I-BABP), a member of the family of intracellular lipid binding proteins, is thought to play a role in the enterohepatic circulation of bile salts. Previously, we have shown by stopped-flow fluorescence analysis that positive binding cooperativity exhibited by I-BABP in its interactions with glycocholate (GCA) and glycochenodeoxycholate (GCDA), the two primary bile salts in humans, is related to a slow conformational change in the protein. In this study, we used backbone (15)N relaxation nuclear magnetic resonance (NMR) techniques to obtain residue-specific information about the internal dynamics of apo I-BABP and the doubly ligated I-BABP:GCA:GCDA complex on various time scales. According to our NMR data, bile salt binding is accompanied by a slight rigidification of the (15)N-(1)H bond vectors on the picosecond to nanosecond time scale, with most pronounced changes occurring in the C-D region. In contrast to the minor effects of ligation on fast motions, relaxation dispersion NMR experiments indicate a marked difference between the two protein states on the microsecond to millisecond time scale. In the apo form, an extensive network of conformational fluctuations is detected throughout segments of the EFGHIJ beta-strands and the C-D loop, which cease upon complexation. Our NMR data are in agreement with a conformational selection model we proposed earlier for I-BABP and support the hypothesis of an allosteric mechanism of ligand binding. According to the NMR measurements, the helical cap region may have a less crucial role in mediating ligand entry and release than what has been indicated for fatty acid binding proteins.
-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>
+Internal motions and exchange processes in human ileal bile acid binding protein as studied by backbone (15)N nuclear magnetic resonance spectroscopy.,Horvath G, Kiraly P, Tarkanyi G, Toke O Biochemistry. 2012 Mar 6;51(9):1848-61. doi: 10.1021/bi201588q. Epub 2012 Feb 27. PMID:22329738<ref>PMID:22329738</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2mm3" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>