2LFO

NMR structure of cl-BABP/SS complexed with glycochenodeoxycholic and glycocholic acids

Summary for 2LFO

• Entry DOI: 10.2210/pdb2lfo/pdb
• Related: 2JN3
• NMR Information: BMRB: 17767
• Descriptor: Fatty acid-binding protein, liver, GLYCOCHOLIC ACID, GLYCOCHENODEOXYCHOLIC ACID (3 entities in total)
• Functional Keywords: heterotypic complex, bile acid binding protein, liver, bile acids, lipid binding protein, disulphide bridge
• Biological source: Gallus gallus (bantam,chickens)
• Cellular location: Cytoplasm: P80226
• Total number of polymer chains: 1
• Total formula weight: 15017.46

Authors

Tomaselli, S.,Cogliati, C.,Pagano, K.,Zetta, L.,Zanzoni, S.,Assfalg, M.,Molinari, H.,Ragona, L. (deposition date: 2011-07-07, release date: 2012-07-11, Last modification date: 2024-10-30)

Primary citation

Tomaselli, S.,Assfalg, M.,Pagano, K.,Cogliati, C.,Zanzoni, S.,Molinari, H.,Ragona, L.
A disulfide bridge allows for site-selective binding in liver bile acid binding protein thereby stabilising the orientation of key amino acid side chains.
Chemistry, 18:2857-2866, 2012

PubMed Abstract: The presence of a disulfide bridge in liver bile acid binding protein (L-BABP/S-S) allows for site-selective binding of two bile acids, glycochenodeoxycholic (GCDA) and glycocholic acid (GCA), differing only in the presence of a hydroxyl group. The protein form devoid of the disulfide bridge (L-BABP) binds both bile salts without discriminating ability. We investigate the determinants of the molecular recognition process in the formation of the heterotypic L-BABP/S-S complex with GCDA [corrected] and GCA [corrected] located in the superficial and inner protein sites, respectively. The comparison of the NMR spectroscopy structure of heterotypic holo L-BABP/S-S, the first reported for this protein family, with that of the homotypic L-BABP complex demonstrates that the introduction of a S-S link between adjacent strands changes the conformation of three key residues, which function as hot-spot mediators of molecular discrimination. The favoured χ(1) rotameric states (t, g(+) and g(-) for E99, Q100 and E109 residues, respectively) allow the onset of an extended intramolecular hydrogen-bond network and the consequent stabilisation of the side-chain orientation of a buried histidine, which is capable of anchoring a specific ligand.

PubMed: 22298334
DOI: 10.1002/chem.201102203

Experimental method

SOLUTION NMR