Human serum albumin (HSA) lipoprotein

Peptides and Backbones Aris Kaksis Riga Stradin's University 2014
     Human serum albumin (HSA) in blood plasma has typical circulating concentration of around 0.6 mM, HSA is the most abundant protein in blood plasma and serves as an important transporter molecule for diphilic lipid-like molecules : hydrophilic group and hydrophobic (nonpolar) group containing molecule in blood plasma water medium.
     HSA greatly increases the solubilising capacity of plasma for its diphilic cargo compounds, allowing them to be present at near millimolar concentrations that are significantly in excess of their aqueous solubilities. The binding capacity of HSA varies widely for different ligands.
1E7G+7 myristic acids, fatty acids transporter HSA
H1,H2,H3,H4,H5,H6,H7,H8,H9,H10,H11,H12,H13,H14,H15,H16,H17,H18,
H19,H20,H21,H22,H23,H24,H25,H26,H27,H28,H29,H30,H31,H32,H33 Backbone thin off
     HSA chain 585 amino acids was split into three domains (Ser5-Gly196,Arg197-Glu383,Pro384-Gly584)1E7G
     Each ~190-residue domain, labeled I H3-G207, II E208-K372 and III V373-G584 from the N terminus, contains 11 helices connected by turns and are structurally very similar to one another.
     66.5 kDa single polypeptide HSA chain consists of 585 amino acids folded 33 individual helices connect 17 disulfide -S-S-bonds to form 9 structural loops.
     The three homologous domains can be further divided into seven(6)-helix IA H1,H2,H3,H4,H5,H6,H7, IIA H12,H13,H14,H15,H16,H17 IIIA H23,H24,H25,H26,H27,H28,H29
and four(5)-helix IB H8,H9,H10,H11 IIB H19,H20,H21,H22 IIIB H30,H31,H32,H3
subdomains termed A and B, which have a common four antiparallel alpha-helix core.
1E7GMarz MYR, 1E7IMarz STE, 1GNJMarz ACD,
2XVVMarz 9DN+MYR, 2XVQMarz 9DS, 2XVWMarz 9NR,
2XW1Marz 9NV, 2XW0Marz 9NF, 2XSIMarz 9NE
Backbone 33 helices strands thin off ,
MYR myristic acid, STE stearate, ACD arachidonic acid,
9DN Dansyl-L-asparagine+MYR,9DS Dansyl-L-sarcosine,9NR Dansyl-L-arginine,
9NV Dansyl-L-norvaline,9NF Dansyl-L-phenylalanine,9NE Dansyl-L-glutamate.
  

Fig.1c.Fatty acid seven binding sites FA1-FA7.
HSA has seven binding sites for long-chain fatty acids, widely considered to be the primary ligand of the protein, labelled FA1-FA7 (Fig. 1c), having variable binding affinities and are formed by residues from all six sub-domains.
     Each of three domains Human serum albumin (HSA) has two primary binding sites for drug molecules. These sites selectively bind different dansylated amino acid compounds, which have long been used as specific markers for the drug pockets on HSA.
     HSA has several distinct binding compartments distributed asymmetrically across the protein and can accommodate a structurally diverse set of ligands. These ligands nevertheless share the general property of being poorly soluble hydrophobic compounds with anionic or electronegative features and include non-esterified fatty acids, thyroxine, uremic toxins, hemin and bilirubin.
H1,H2,H3,H4,H5,H6,H7,H8,H9,H10,H11,H12,H13,H14,H15,H16,H17,H18,
H19,H20,H21,H22,H23,H24,H25,H26,H27,H28,H29,H30,H31,H32,H33 Backbone thin off
1HK1 L-thyroxin+T4D, 1O9X heme+HEM+IBP, 2VUE BiliRubin+BLA,
2BXD r-warfarin+RWF, anticoagulant drug;
2BXE diflunisal+1FL, salicylate derivative nonsteroidal anti-inflammatory agent NSAIA;
2BXG ibuprofen+IBP, nonsteroidal anti-inflammatory agent NSAIA;
2BXM indoMetacyn+IMN, nonsteroidal anti-inflammatory agent NSAIA;
2BXC phenyl Butazon+P1Z, nonsteroidal anti-inflammatory,antipyretic,analgesic;
2I2Z salicyl MYR+salicyl+MYR, 2BXL salicyl Jod+salicyl, Salicilic-2-hydroxy-benzoic Acid
2BXF diazepam+DZP, anticonvulsant,anxiolytic,sedative,relaxant,amnesic
2VUF fusidic+FUA, Fusidic Acid antibiotic Anti-Bacterial Agent,Protein Synthesis Inhibitor;
6MDQ 2 testosterons+TES1-2, testosteron binding sites TS1 and TS2
References
1. J Struct Biol. 2011 Apr;174(1):84-91.
2XVQ;2BXA;1E7G; 2XVQ;2XW1;2XW0;2XVU;2XVV;2XVW;2XS
2. Bioinformatics (2011) 27 (13): 1806-1813.
2BXD;2BXA;2BX8;3B9L;3LU6;3LU7;2XVW;2XVU;2XSI;2BXL;2BXM;2BXN;2BXB
3. BMC Struct Biol. 2014 Jan 23;14:4. doi: 10.1186/1472-6807-14-4.
4BKE;2BXF [38],2XW1 [3],2XVQ [3],2XW0
4. J Mol Biol. 2008 Aug 29;381(2):394-406.
2VUE;HSA-4Z,15E-Bilirubin-IXα; 2VUF;HSA-fusidic acid;2BXA
5. BMC Struct Biol. BMC Struct Biol. 2003; 3: 6.
1O9X MYR,Heme; 1N5U; 4MBN; 1E7G
6. J Mol Biol. 2005 Oct 14;353(1):38-52.
2BXG (12); ibuprofen,heme1O9X (23), 1H9Z(20)
7. Chem Sci. 2019 Feb 14; 10(6): 1607–1618.
TES, 6MDQ

Original source ChemScape Chime view:
Eric Marz (1997) Massachusetts University USA