title: Binding of V(IV)O²⁺ to the Fe binding sites of human serum transferrin. A theoretical study.
abstract: The binding of V(IV)O²⁺ to human serum transferrin (hTF) at the FeIII binding sites is addressed. Geometry optimization calculations were performed for the binding of V(IV)O²⁺ to the N-terminal lobe of hTF (hTFN), and indicate that in the presence of CO₃²⁻ or HCO₃ −, V(IV) is bound to five atoms in a distorted geometry. The structures of V(IV)O-hTFN species optimized at the semiempirical level were also used to calculate the ⁵¹V and ¹⁴N A tensors by density functional theory methods, and were compared with the reported experimental values. Globally, of all the calculated V(IV)O-hTF structures, the one that yields the lowest calculated heats of formation and minimum deviations from the experimental values of the ⁵¹V and ¹⁴N A tensor components is the structure that includes CO₃²⁻ as a synergistic anion. In this structure the V=O bond length is approximately 1.6 Å, and the vanadium atom is also coordinated to the phenolate oxygen atom of Tyr188 (at approximately 1.9 Å), the aspartate oxygen atom of Asp63 (at approximately 1.9 Å), the His249 Nτ atom (at approximately 2.1 Å), and a carbonate oxygen atom (at approximately 1.8 Å). The Tyr95 phenolic ocygen atom is approximately 3.3 Å from the metal center, and thus is very weakly bound to V(IV). All of these oxygen atoms are able to establish dipolar interactions with groups of the protein.
authors: Gonçalo C
authors: GC
authors: Justino
authors: Eugenio
authors: E
authors: Garribba
authors: João Costa
authors: JC
authors: Pessoa
mesh_terms: D001665:Binding Sites; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011789:Quantum Theory; D013816:Thermodynamics; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism*; D014638:Vanadates / Q000378:metabolism*
chemical_list: D014168:Transferrin; C075743:oxovanadium IV; D014638:Vanadates; D007501:Iron
references: Biochem J. 1980 Feb 1;185(2):483-8
references: 7396826
references: Crit Rev Oncol Hematol. 2002 Jun;42(3):249-65
references: 12050018
references: Biochim Biophys Acta. 2012 Mar;1820(3):282-90
references: 22155077
references: J Inorg Biochem. 2004 Jun;98(6):959-68
references: 15149802
references: Org Biomol Chem. 2012 Aug 21;10(31):6341-9
references: 22751934
references: Dalton Trans. 2009 Mar 21;(11):1914-8
references: 19259560
references: J Inorg Biochem. 2000 May 30;80(1-2):65-73
references: 10885465
references: J Biol Inorg Chem. 2012 Jun;17(5):773-90
references: 22526563
references: Chem Rev. 1999 Sep 8;99(9):2817-42
references: 11749502
references: Metallomics. 2010 Feb;2(2):154-61
references: 21069147
references: J Inorg Biochem. 2009 Apr;103(4):648-55
references: 19201482
references: J Biol Inorg Chem. 2002 Sep;7(7-8):884-90
references: 12203026
references: J Chem Theory Comput. 2011 Feb 8;7(2):525-37
references: 26596171
references: Dalton Trans. 2009 Apr 7;(13):2428-37
references: 19290378
references: Analyst. 2004 Jan;129(1):51-4
references: 14737583
references: Inorg Chem. 2011 Feb 7;50(3):883-99
references: 21226475
references: J Biol Inorg Chem. 2010 Aug;15(6):825-39
references: 20339887
references: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W665-7
references: 15215472
references: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W522-5
references: 17488841
references: Metallomics. 2012 Jan;4(1):33-6
references: 22094980
references: J Inorg Biochem. 2009 Oct;103(10):1386-94
references: 19695708
references: Dalton Trans. 2010 Jan 7;(1):212-20
references: 20023952
references: Proteins. 2008 Nov 15;73(3):765-83
references: 18498103
references: J Inorg Biochem. 2012 Oct;115:87-99
references: 22926028
references: J Inorg Biochem. 2009 Apr;103(4):643-7
references: 19056126
references: Biochemistry. 1998 Jun 2;37(22):7919-28
references: 9609685
references: J Inorg Biochem. 2000 Jan 30;78(2):97-108
references: 10766332
references: J Mol Model. 2007 Dec;13(12):1173-213
references: 17828561
references: J Biol Chem. 1989 Mar 25;264(9):4776-81
references: 2538460
references: Inorg Chem. 2010 Jan 4;49(1):174-87
references: 19947643
references: J Am Chem Soc. 2005 Apr 13;127(14):5104-15
references: 15810845
references: Curr Med Chem. 2010;17(31):3701-38
references: 20846109
references: Coord Chem Rev. 2011 Oct;255(19-20):2258-2269
references: 23049138
references: J Biol Chem. 2006 Aug 25;281(34):24934-44
references: 16793765
references: J Comput Chem. 2011 Oct;32(13):2822-35
references: 21735449
references: J Inorg Biochem. 2005 Feb;99(2):443-51
references: 15621276
references: J Inorg Biochem. 2013 Apr;121:187-95
references: 23411030
references: Inorg Chem. 2009 Apr 20;48(8):3542-61
references: 19290614
references: J Phys Chem B. 1999 Dec 2;103(48):10627-31
references: 16467924
references: Dalton Trans. 2010 Feb 7;39(5):1345-60
references: 20104362
references: Chemistry. 2010 Jul 19;16(27):8167-80
references: 20533466
references: Inorg Chem. 2009 Jul 6;48(13):5747-57
references: 19514735
references: J Chem Theory Comput. 2011 Jul 12;7(7):2284-95
references: 26606496
references: J Mol Model. 2009 Jul;15(7):765-805
references: 19066990
references: Inorg Chem. 2011 Apr 18;50(8):3717-28
references: 21434616
references: Proteins. 2005 Dec 1;61(4):704-21
references: 16231289
references: Biochemistry. 1991 Sep 24;30(38):9210-6
references: 1654090