title: Stereo-selectivity of human serum albumin to enantiomeric and isoelectronic pollutants dissected by spectroscopy, calorimetry and bioinformatics.
abstract: 1-naphthol (1N), 2-naphthol (2N) and 8-quinolinol (8H) are general water pollutants. 1N and 2N are the configurational enantiomers and 8H is isoelectronic to 1N and 2N. These pollutants when ingested are transported in the blood by proteins like human serum albumin (HSA). Binding of these pollutants to HSA has been explored to elucidate the specific selectivity of molecular recognition by this multiligand binding protein. The association constants (K(b)) of these pollutants to HSA were moderate (10(4)-10(5) M(-1)). The proximity of the ligands to HSA is also revealed by their average binding distance, r, which is estimated to be in the range of 4.39-5.37 nm. The binding free energy (ΔG) in each case remains effectively the same for each site because of enthalpy-entropy compensation (EEC). The difference observed between ΔC(p) (exp) and ΔC(p) (calc) are suggested to be caused by binding-induced flexibility changes in the HSA. Efforts are also made to elaborate the differences observed in binding isotherms obtained through multiple approaches of calorimetry, spectroscopy and bioinformatics. We suggest that difference in dissociation constants of pollutants by calorimetry, spectroscopic and computational approaches could correspond to occurrence of different set of populations of pollutants having different molecular characteristics in ground state and excited state. Furthermore, our observation of enhanced binding of pollutants (2N and 8H) in the presence of hemin signifies that ligands like hemin may enhance the storage period of these pollutants in blood that may even facilitate the ill effects of these pollutants.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Ejaz
authors.initials: E
authors.lastname: Ahmad
authors.forename: Gulam
authors.initials: G
authors.lastname: Rabbani
authors.forename: Nida
authors.initials: N
authors.lastname: Zaidi
authors.forename: Saurabh
authors.initials: S
authors.lastname: Singh
authors.forename: Mohd
authors.initials: M
authors.lastname: Rehan
authors.forename: Mohd Moin
authors.initials: MM
authors.lastname: Khan
authors.forename: Shah Kamranur
authors.initials: SK
authors.lastname: Rahman
authors.forename: Zainuddin
authors.initials: Z
authors.lastname: Quadri
authors.forename: Mohd
authors.initials: M
authors.lastname: Shadab
authors.forename: Mohd Tashfeen
authors.initials: MT
authors.lastname: Ashraf
authors.forename: Naidu
authors.initials: N
authors.lastname: Subbarao
authors.forename: Rajiv
authors.initials: R
authors.lastname: Bhat
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D002151:Calorimetry / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel; D004785:Environmental Pollutants / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D004785:Environmental Pollutants; D012709:Serum Albumin
references.citation: J Biochem. 2010 Feb;147(2):191-200
references.pmid: 19884191
references.citation: J Comput Chem. 2009 Dec;30(16):2785-91
references.pmid: 19399780
references.citation: Epidemiology. 2006 Jan;17(1):61-8
references.pmid: 16357596
references.citation: J Biol Chem. 2001 Jun 22;276(25):22804-9
references.pmid: 11285262
references.citation: J Mol Recognit. 1999 Jan-Feb;12(1):3-18
references.pmid: 10398392
references.citation: Anal Chem. 1990 Oct 1;62(19):2114-22
references.pmid: 2256548
references.citation: Mol Pharmacol. 1975 Nov;11(6):824-32
references.pmid: 1207674
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2005 Feb;61(4):629-36
references.pmid: 15649793
references.citation: Protein Eng. 1995 Feb;8(2):127-34
references.pmid: 7630882
references.citation: Biochem J. 1991 Feb 1;273 ( Pt 3):641-4
references.pmid: 1996962
references.citation: J Comput Aided Mol Des. 2002 Jan;16(1):11-26
references.pmid: 12197663
references.citation: Talanta. 1998 Dec;47(5):1223-9
references.pmid: 18967427
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14828-33
references.pmid: 14657388
references.citation: Biochem Pharmacol. 1985 Sep 15;34(18):3299-304
references.pmid: 4038338
references.citation: J Mol Biol. 2002 Jan 25;315(4):845-57
references.pmid: 11812152
references.citation: J Biol Chem. 2000 Jul 14;275(28):20985-95
references.pmid: 10764755
references.citation: Biophys Chem. 2008 Feb;132(2-3):81-8
references.pmid: 18037556
references.citation: Langmuir. 2008 Sep 16;24(18):10235-9
references.pmid: 18700748
references.citation: J Biol Chem. 1999 Oct 8;274(41):29303-10
references.pmid: 10506189
references.citation: J Comput Chem. 2004 Oct;25(13):1605-12
references.pmid: 15264254
references.citation: Biochem J. 1980 Oct 1;191(1):95-102
references.pmid: 7470101
references.citation: Protein Eng. 1999 Jun;12(6):439-46
references.pmid: 10388840
references.citation: Science. 1994 Feb 11;263(5148):777-84
references.pmid: 8303294
references.citation: J Biol Chem. 2000 Dec 8;275(49):38731-8
references.pmid: 10940303
references.citation: Chem Biol. 1997 Mar;4(3):215-21
references.pmid: 9115415
references.citation: Nat Struct Biol. 1996 Jul;3(7):626-31
references.pmid: 8673607
references.citation: Adv Protein Chem. 1992;43:313-61
references.pmid: 1442323
references.citation: Biophys J. 1998 Aug;75(2):1084-96
references.pmid: 9675210
references.citation: J Mol Recognit. 2008 Sep-Oct;21(5):289-312
references.pmid: 18729242
references.citation: J Mol Biol. 2005 Oct 14;353(1):38-52
references.pmid: 16169013
references.citation: J Phys Chem B. 2006 May 18;110(19):9728-37
references.pmid: 16686525
references.citation: J Biol Chem. 1969 Apr 25;244(8):1961-7
references.pmid: 4889460
references.citation: J Struct Biol. 2009 Jan;165(1):10-8
references.pmid: 18929667
references.citation: Dan Med Bull. 1990 Feb;37(1):57-84
references.pmid: 2155760
references.citation: Biochemistry. 1981 May 26;20(11):3096-102
references.pmid: 7248271
references.citation: Biophys J. 1986 Sep;50(3):507-12
references.pmid: 3756301
references.citation: Methods Enzymol. 1986;131:4-51
references.pmid: 3773768