Decrease in stability of human albumin with increase in protein concentration.


Abstract

The stability (reflected in denaturation temperature, Td) of defatted human albumin monomer, monitored by differential scanning calorimetry, decreases with increasing protein concentration. This is shown to be compatible with a simple model in which reversible polymerization of denatured monomer promotes unfolding. This model also predicts an increase in transition cooperativity with decreasing protein concentration whereas experimentally cooperativity decreases because the rate of thermally induced polymerization of unfolded monomer is slow relative to the scan rate of the calorimeter. The denaturation of undefatted human albumin monomer, subsaturated with high affinity endogenous long-chain fatty acid (LCFA), was previously observed by differential scanning calorimetry to be a biphasic process. Td for the first endotherm, associated with the denaturation of LCFA-poor species, decreases with increasing protein concentration similar to that for defatted monomer whereas Td for the second endotherm, associated with denaturation of LCFA-rich species, is independent of concentration. The magnitude of the concentration dependence of Td relates directly to the extent of polymerization of denatured monomer, which decreases with increasing level of bound ligand. The bimodal thermogram observed for undefatted monomer persists upon simultaneous extrapolation of Td values to low concentration and low scan rate thereby demonstrating that this biphasic denaturation arising from ligand redistribution during denaturation is a true thermodynamic phenomenon and not an artifact of specific experimental conditions or the method used to induce denaturation. Study holds ProTherm entries: 5140 Extra Details: denatured monomer; cooperativity; long-chain fatty acid;,thermodynamic phenomenon

Submission Details

ID: etyr8erc

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:28 p.m.

Version: 1

Publication Details
Ross PD;Shrake A,J. Biol. Chem. (1988) Decrease in stability of human albumin with increase in protein concentration. PMID:3403521
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1YSX 2005-06-07 Solution structure of domain 3 from human serum albumin complexed to an anti-apoptotic ligand directed against Bcl-xL and Bcl-2
2N0X 2015-04-29 Three dimensional structure of EPI-X4, a human albumin-derived peptide that regulates innate immunity through the CXCR4/CXCL12 chemotactic axis and antagonizes HIV-1 entry
2ESG 2006-01-31 Solution structure of the complex between immunoglobulin IgA1 and human serum albumin
1N5U 2003-06-24 1.9 X-RAY STUDY OF HUMAN SERUM ALBUMIN COMPLEXED WITH HEME
4L8U 2013-07-24 2.01 X-ray study of human serum albumin complexed with 9 amino camptothecin
3SQJ 2011-11-02 2.05 Recombinant human serum albumin from transgenic plant
5Z0B 2018-12-19 2.17 Crystal structure of plasma-derived human serum albumin
4Z69 2016-01-27 2.19 Human serum albumin complexed with palmitic acid and diclofenac
3A73 2010-01-19 2.19 Crystal Structure Analysis of Human serum albumin complexed with delta 12-prostaglandin J2
3UIV 2012-11-07 2.2 Human serum albumin-myristate-amantadine hydrochloride complex
1E7A 2001-01-17 2.2 Crystal structure of human serum albumin complexed with the general anesthetic propofol
4G03 2013-07-10 2.22 High-resolution Crystal Structural Variance Analysis between Recombinant and Wild-type Human Serum Albumin
2BXH 2005-09-22 2.25 Human serum albumin complexed with indoxyl sulfate
5ID7 2016-05-11 2.26 Crystal structure of human serum albumin in complex with phosphorodithioate derivative of myristoyl cyclic phosphatidic acid (cPA)
6A7P 2018-10-24 2.28 Human serum albumin complexed with aripiprazole
4E99 2012-06-06 2.3 Human Serum Albumin Complex with Perfluorooctane Sulfonate Potassium
2BXP 2005-09-22 2.3 Human serum albumin complexed with myristate and phenylbutazone
4G04 2013-07-10 2.3 High-resolution Crystal Structural Variance Analysis between Recombinant and Wild-type Human Serum Albumin
4EMX 2012-04-25 2.3 Crystal structure analysis of Human Serum Albumin in complex with chloride anions at cryogenic temperature
3JRY 2010-04-21 2.3 Human Serum albumin with bound Sulfate
4HGM 2013-05-08 2.34 Shark IgNAR Variable Domain
4BKE 2014-02-05 2.35 Recombinant human serum albumin with palmitic acid. Synthetic cationic antimicrobial peptides bind with their hydrophobic parts to drug site II of human serum albumin
2BXA 2005-09-22 2.35 Human serum albumin complexed with 3-carboxy-4-methyl-5-propyl-2- furanpropanoic acid (CMPF)
1E7B 2001-01-17 2.38 Crystal structure of human serum albumin complexed with the general anesthetic halothane
6EZQ 2017-12-13 2.39 human Serum Albumin complexed with NBD-C12 fatty acid
2BXK 2005-09-22 2.4 Human serum albumin complexed with myristate, azapropazone and indomethacin
2XVV 2010-11-10 2.4 Human serum albumin complexed with dansyl-L-asparagine and myristic acid
1GNI 2002-01-01 2.4 HUMAN SERUM ALBUMIN COMPLEXED WITH cis-9-OCTADECENOIC ACID (OLEIC ACID)
4K71 2013-10-23 2.4 Crystal structure of a high affinity Human Serum Albumin variant bound to the Neonatal Fc Receptor
1E7C 2001-01-17 2.4 HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID and the general anesthetic halothane
1HK4 2003-05-16 2.4 HUMAN SERUM ALBUMIN COMPLEXED WITH THYROXINE (3,3',5,5'-TETRAIODO-L-THYRONINE) and myristic acid (tetradecanoic acid)
2XW0 2010-11-10 2.4 Human serum albumin complexed with dansyl-L-phenylalanine
4L9K 2013-07-24 2.4 X-ray study of human serum albumin complexed with camptothecin
4LA0 2013-07-24 2.4 X-ray study of human serum albumin complexed with bicalutamide
4IW2 2013-04-24 2.41 HSA-glucose complex
2VUE 2008-06-17 2.42 Human serum albumin complexed with 4Z,15E-bilirubin-IX-alpha
1E7F 2000-11-06 2.43 HUMAN SERUM ALBUMIN COMPLEXED WITH DODECANOIC ACID (LAURIC ACID)
1E7H 2000-12-08 2.43 HUMAN SERUM ALBUMIN COMPLEXED WITH HEXADECANOIC ACID (PALMITIC ACID)
2XW1 2010-11-10 2.5 Human serum albumin complexed with dansyl-L-norvaline
1AO6 1998-05-27 2.5 CRYSTAL STRUCTURE OF HUMAN SERUM ALBUMIN
1E7G 2000-11-06 2.5 Human serum albumin complexed with tetradecanoic acid (myristic acid)
1E7E 2000-11-06 2.5 HUMAN SERUM ALBUMIN COMPLEXED WITH DECANOIC ACID (CAPRIC ACID)
1BJ5 1998-11-04 2.5 HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID
1H9Z 2001-06-20 2.5 Human Serum Albumin Complexed With Myristic Acid and the R-(+) enantiomer of warfarin
2BXM 2005-09-22 2.5 Human serum albumin complexed with myristate and indomethacin
1BM0 1999-07-28 2.5 CRYSTAL STRUCTURE OF HUMAN SERUM ALBUMIN
2BXI 2005-09-22 2.5 Human serum albumin complexed with myristate and azapropazone
1HA2 2001-06-20 2.5 Human Serum Albumin Complexed With Myristic Acid and the S-(-) enantiomer of warfarin
2VDB 2008-02-26 2.52 Structure of human serum albumin with S-naproxen and the GA module
5GIY 2017-07-19 2.54 HSA-Palmitic acid-[RuCl5(ind)]2-
4IW1 2013-04-24 2.56 HSA-fructose complex
1E78 2001-03-23 2.6 Crystal structure of human serum albumin
1GNJ 2002-01-01 2.6 HUMAN SERUM ALBUMIN COMPLEXED WITH cis-5,8,11,14-EICOSATETRAENOIC ACID (ARACHIDONIC ACID)
2BXO 2005-09-22 2.6 Human serum albumin complexed with myristate and oxyphenbutazone
5VNW 2018-02-21 2.6 Crystal structure of Nb.b201 bound to human serum albumin
3B9L 2008-05-27 2.6 Human serum albumin complexed with myristate and AZT
3LU8 2010-10-27 2.6 Human serum albumin in complex with compound 3
2BXL 2005-09-22 2.6 Human serum albumin complexed with myristate and 3,5-diiodosalicylic acid
3TDL 2012-06-27 2.6 Structure of human serum albumin in complex with DAUDA
2XVU 2010-11-10 2.6 Human serum albumin complexed with dansyl-L-asparagine
2BXQ 2005-09-22 2.6 Human serum albumin complexed with myristate, phenylbutazone and indomethacin
5YB1 2018-09-05 2.62 Structure and function of human serum albumin-metal agent complex
5YOQ 2018-02-07 2.65 Human serum albumin complexed with sodium 4-phenylbutyrate
2XVW 2010-11-10 2.65 Human serum albumin complexed with dansyl-L-arginine and myristic acid
2BXN 2005-09-22 2.65 Human serum albumin complexed with myristate and iodipamide
5IJF 2016-03-16 2.65 Crystal structure of Human Serum Albumin in the presence of 0.5 mM zinc at pH 9.0
1HK1 2003-05-16 2.65 HUMAN SERUM ALBUMIN COMPLEXED WITH THYROXINE (3,3',5,5'-TETRAIODO-L-THYRONINE)
1HK5 2003-05-16 2.7 HUMAN SERUM ALBUMIN MUTANT R218H COMPLEXED WITH THYROXINE (3,3',5,5'-TETRAIODO-L-THYRONINE) and myristic acid (tetradecanoic acid)
2BX8 2005-09-22 2.7 Human serum albumin complexed with azapropazone
5UJB 2017-05-03 2.7 Structure of a Mcl-1 Inhibitor Binding to Site 3 of Human Serum Albumin
2BXG 2005-09-22 2.7 Human serum albumin complexed with ibuprofen
3B9M 2008-05-27 2.7 Human serum albumin complexed with myristate, 3'-azido-3'-deoxythymidine (AZT) and salicylic acid
4L9Q 2013-07-24 2.7 X-ray study of human serum albumin complexed with teniposide
1TF0 2004-09-07 2.7 Crystal structure of the GA module complexed with human serum albumin
2I2Z 2006-12-12 2.7 Human serum albumin complexed with myristate and aspirin
2XSI 2010-11-10 2.7 Human serum albumin complexed with dansyl-L-glutamate and myristic acid
1E7I 2000-11-06 2.7 HUMAN SERUM ALBUMIN COMPLEXED WITH OCTADECANOIC ACID (STEARIC ACID)
3LU6 2010-10-27 2.7 Human serum albumin in complex with compound 1
4LB9 2013-07-24 2.7 X-ray study of human serum albumin complexed with etoposide
2YDF 2011-04-27 2.75 HUMAN SERUM ALBUMIN COMPLEXED WITH IOPHENOXIC ACID
1HK2 2003-05-16 2.8 HUMAN SERUM ALBUMIN MUTANT R218H COMPLEXED WITH THYROXINE (3,3',5,5'-TETRAIODO-L-THYRONINE)
3LU7 2010-10-27 2.8 Human serum albumin in complex with compound 2
3CX9 2009-04-28 2.8 Crystal Structure of Human serum albumin complexed with Myristic acid and lysophosphatidylethanolamine
5GIX 2017-07-19 2.8 Human serum albumin-Palmitic acid-Fe(Hn3piT)Cl2
4LB2 2013-07-24 2.8 X-ray study of human serum albumin complexed with idarubicin
1UOR 1998-05-27 2.8 X-RAY STUDY OF RECOMBINANT HUMAN SERUM ALBUMIN. PHASES DETERMINED BY MOLECULAR REPLACEMENT METHOD, USING LOW RESOLUTION STRUCTURE MODEL OF TETRAGONAL FORM OF HUMAN SERUM ALBUMIN
1HK3 2003-05-16 2.8 Human serum albumin mutant r218p complexed with thyroxine (3,3',5,5'-tetraiodo-l-thyronine)
2XVQ 2010-11-10 2.9 Human serum albumin complexed with dansyl-L-sarcosine
2I30 2006-12-12 2.9 Human serum albumin complexed with myristate and salicylic acid
2BXE 2005-09-22 2.95 Human serum albumin complexed with diflunisal
2BXF 2005-09-22 2.95 Human serum albumin complexed with diazepam
5X52 2017-05-17 3.01 Human serum albumin complexed with octanoate and N-acetyl-L-methionine
4N0F 2014-02-05 3.02 Human FcRn complexed with human serum albumin
4HGK 2013-05-08 3.04 Shark IgNAR variable domain
2BXD 2005-09-22 3.05 Human serum albumin complexed with warfarin
2VUF 2008-06-24 3.05 Human serum albumin complexed with fusidic acid
2BXC 2005-09-22 3.1 Human serum albumin complexed with phenylbutazone
1BKE 1999-01-13 3.15 HUMAN SERUM ALBUMIN IN A COMPLEX WITH MYRISTIC ACID AND TRI-IODOBENZOIC ACID
4S1Y 2015-04-29 3.16 X-ray structure of human serum albumin complexed with cisplatin
2BXB 2005-09-22 3.2 Human serum albumin complexed with oxyphenbutazone
5IFO 2016-06-01 3.2 X-ray structure of HSA-Myr-KP1019
1O9X 2003-03-13 3.2 HUMAN SERUM ALBUMIN COMPLEXED WITH TETRADECANOIC ACID (MYRISTIC ACID) AND HEMIN
4K2C 2013-05-01 3.23 HSA Ligand Free
3JQZ 2010-04-21 3.3 Crystal Structure of Human serum albumin complexed with Lidocaine
5FUO 2016-06-29 3.6 Extending the half-life of a Fab fragment through generation of a humanised anti-Human Serum Albumin (HSA) Fv domain: an investigation into the correlation between affinity and serum half-life
4N0U 2014-02-05 3.8 Ternary complex between Neonatal Fc receptor, serum albumin and Fc
6JE7 2019-03-27 3.9 Crystal structure of human serum albumin crystallized by ammonium sulfate

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
93.7 Serum albumin Q28522 ALBU_MACMU
93.7 Serum albumin A2V9Z4 ALBU_MACFA
98.5 SERUM ALBUMIN Q5NVH5 ALBU_PONAB
100.0 SERUM ALBUMIN P02768 ALBU_HUMAN