title: Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin.
abstract: Human serum albumin (HSA), the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s). As a matter of fact, HSA is a major transport protein in the bloodstream and the regulation of the functional allosteric interrelationships between the different binding sites represents a fundamental information for the knowledge of its transport function. Here, kinetics and thermodynamics of the allosteric modulation: (i) of carbon monoxide (CO) binding to ferrous human serum heme-albumin (HSA-heme-Fe(II)) by warfarin (WF), and (ii) of WF binding to HSA-heme-Fe(II) by CO are reported. All data were obtained at pH 7.0 and 25°C. Kinetics of CO and WF binding to the FA1 and FA7 sites of HSA-heme-Fe(II), respectively, follows a multi-exponential behavior (with the same relative percentage for the two ligands). This can be accounted for by the existence of multiple conformations and/or heme-protein axial coordination forms of HSA-heme-Fe(II). The HSA-heme-Fe(II) populations have been characterized by resonance Raman spectroscopy, indicating the coexistence of different species characterized by four-, five- and six-coordination of the heme-Fe atom. As a whole, these results suggest that: (i) upon CO binding a conformational change of HSA-heme-Fe(II) takes place (likely reflecting the displacement of an endogenous ligand by CO), and (ii) CO and/or WF binding brings about a ligand-dependent variation of the HSA-heme-Fe(II) population distribution of the various coordinating species. The detailed thermodynamic and kinetic analysis here reported allows a quantitative description of the mutual allosteric effect of CO and WF binding to HSA-heme-Fe(II).
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, Roma, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Bocedi
authors.forename: Giampiero
authors.initials: G
authors.lastname: De Sanctis
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaccio
authors.forename: Grazia R
authors.initials: GR
authors.lastname: Tundo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Masi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fanali
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Nicoletti
authors.forename: Mauro
authors.initials: M
authors.lastname: Fasano
authors.forename: Giulietta
authors.initials: G
authors.lastname: Smulevich
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
mesh_terms: D000494:Allosteric Regulation; D002248:Carbon Monoxide / Q000378:metabolism*; D005296:Ferrous Compounds / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics; D014859:Warfarin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005296:Ferrous Compounds; D012709:Serum Albumin; D006418:Heme; D014859:Warfarin; D002248:Carbon Monoxide
references.citation: J Am Chem Soc. 2005 Nov 16;127(45):15933-42
references.pmid: 16277537
references.citation: Pharm Res. 2002 Oct;19(10):1458-64
references.pmid: 12425462
references.citation: Mol Pharmacol. 1975 Nov;11(6):824-32
references.pmid: 1207674
references.citation: Biophys J. 1999 Aug;77(2):1143-9
references.pmid: 10423459
references.citation: Mini Rev Med Chem. 2006 Apr;6(4):483-9
references.pmid: 16613585
references.citation: J Mol Biol. 2000 Nov 10;303(5):721-32
references.pmid: 11061971
references.citation: Mol Aspects Med. 2012 Jun;33(3):209-90
references.pmid: 22230555
references.citation: Protein Sci. 2000 Aug;9(8):1455-65
references.pmid: 10975567
references.citation: Vox Sang. 2002 Aug;83 Suppl 1:315-9
references.pmid: 12617161
references.citation: Biochem Biophys Res Commun. 2009 Sep 11;387(1):83-6
references.pmid: 19559669
references.citation: Biochim Biophys Acta. 2001 Jun 11;1547(2):302-12
references.pmid: 11410286
references.citation: Chirality. 2002 May 15;14(5):442-8
references.pmid: 11984760
references.citation: Biochem Biophys Res Commun. 2002 Mar 8;291(4):813-9
references.pmid: 11866438
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Protein Eng. 1999 Jun;12(6):439-46
references.pmid: 10388840
references.citation: IUBMB Life. 2008 Feb;60(2):112-23
references.pmid: 18380000
references.citation: PLoS One. 2011;6(11):e26186
references.pmid: 22073150
references.citation: J Biol Chem. 1985 Apr 10;260(7):4151-5
references.pmid: 3980472
references.citation: J Inorg Biochem. 2005 Jan;99(1):34-44
references.pmid: 15598489
references.citation: IUBMB Life. 2005 Dec;57(12):787-96
references.pmid: 16393781
references.citation: J Biol Chem. 2000 Dec 8;275(49):38731-8
references.pmid: 10940303
references.citation: J Mol Biol. 2005 Oct 14;353(1):38-52
references.pmid: 16169013
references.citation: PLoS One. 2012;7(6):e38372
references.pmid: 22685563
references.citation: Biochem Biophys Res Commun. 2008 May 2;369(2):686-91
references.pmid: 18307975
references.citation: Pharm Res. 2004 Feb;21(2):285-92
references.pmid: 15032310
references.citation: J Biol Chem. 2001 Jun 22;276(25):22804-9
references.pmid: 11285262
references.citation: Biochim Biophys Acta. 1981 Jul 28;669(2):244-50
references.pmid: 7284438
references.citation: Biochem Biophys Res Commun. 2007 Feb 9;353(2):469-74
references.pmid: 17188651
references.citation: J Mol Biol. 2006 Oct 27;363(3):702-12
references.pmid: 16979183
references.citation: J Biol Inorg Chem. 2002 Mar;7(3):273-83
references.pmid: 11935351
references.citation: Biotechnol Appl Biochem. 2000 Apr;31(2):101-6
references.pmid: 10744954
references.citation: Biochemistry. 1968 Jun;7(6):2172-82
references.pmid: 5690710
references.citation: Biofactors. 2012 Jan-Feb;38(1):1-13
references.pmid: 22213392
references.citation: J Pharm Sci. 1989 Mar;78(3):195-9
references.pmid: 2724076
references.citation: J Mol Biol. 2008 Aug 29;381(2):394-406
references.pmid: 18602119
references.citation: J Biol Inorg Chem. 2012 Jan;17(1):133-47
references.pmid: 21894504
references.citation: FEBS J. 2005 Sep;272(18):4672-83
references.pmid: 16156788
references.citation: Mol Pharmacol. 1976 Nov;12(6):1052-61
references.pmid: 1004490
references.citation: J Mol Biol. 2006 Aug 11;361(2):336-51
references.pmid: 16844140
references.citation: IUBMB Life. 2012 May;64(5):378-86
references.pmid: 22431507
references.citation: Biochem Biophys Res Commun. 2005 Aug 26;334(2):481-6
references.pmid: 16004963
references.citation: IUBMB Life. 2009 Dec;61(12):1118-22
references.pmid: 19946891
references.citation: BMC Struct Biol. 2003 Jul 7;3:6
references.pmid: 12846933
references.citation: Adv Protein Chem. 1994;45:153-203
references.pmid: 8154369
references.citation: Biophys Chem. 2010 May;148(1-3):16-22
references.pmid: 20346571
references.citation: J Biol Inorg Chem. 2001 Jun;6(5-6):650-8
references.pmid: 11472028
references.citation: J Am Chem Soc. 2008 Sep 3;130(35):11677-88
references.pmid: 18681435
references.citation: FEBS J. 2007 Sep;274(17):4491-502
references.pmid: 17725715
references.citation: Proc Natl Acad Sci U S A. 2003 May 27;100(11):6440-5
references.pmid: 12743361
references.citation: Eur J Biochem. 1996 Jan 15;235(1-2):49-53
references.pmid: 8631366
references.citation: Ann Intern Med. 2012 Dec 4;157(11):796-807
references.pmid: 22928173
references.citation: Biochem Mol Biol Educ. 2005 May;33(3):169-76
references.pmid: 21638571
references.citation: Biochim Biophys Acta. 1999 Jul 13;1432(2):313-23
references.pmid: 10407153
references.citation: J Biol Chem. 1980 Apr 10;255(7):3032-7
references.pmid: 7358725
references.citation: Eur J Biochem. 2001 Dec;268(23):6214-20
references.pmid: 11733017
references.citation: IUBMB Life. 2007 Jul;59(7):436-40
references.pmid: 17654119
references.citation: Curr Med Chem. 2002 Aug;9(15):1463-81
references.pmid: 12173977
references.citation: FEBS J. 2005 Dec;272(24):6287-96
references.pmid: 16336266
references.citation: Chirality. 1999;11(2):115-20
references.pmid: 9951402
references.citation: J Biol Chem. 1967 Jan 25;242(2):173-81
references.pmid: 6016603
references.citation: Biol Pharm Bull. 2002 Jun;25(6):695-704
references.pmid: 12081132
references.citation: Hum Mutat. 2008 Aug;29(8):1007-16
references.pmid: 18459107
references.citation: FEBS J. 2009 Apr;276(8):2241-50
references.pmid: 19298387
references.citation: Nat Struct Biol. 1998 Sep;5(9):827-35
references.pmid: 9731778
references.citation: Nature. 1992 Jul 16;358(6383):209-15
references.pmid: 1630489