6xv0

lauric acid functionalized hexamolybdoaluminate bound to human serum albuminlauric acid functionalized hexamolybdoaluminate bound to human serum albumin

Structural highlights

6xv0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ALBU_HUMAN Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:103600. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.^[1] ^[2] ^[3] ^[4]

Function

ALBU_HUMAN Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.^[5]

Publication Abstract from PubMed

The Anderson-type hexamolybdoaluminate functionalized with lauric acid (LA), (TBA)3[Al(OH)3Mo6O18{(OCH2)3CNHCOC11H23}].9H2O (TBA-AlMo6-LA, where TBA = tetrabutylammonium), was prepared via two synthetic routes and characterized by thermogravimetric and elemental analyses, mass spectrometry, IR and (1)H NMR spectroscopy, and powder and single-crystal X-ray diffraction. The interaction of TBA-AlMo6-LA with human serum albumin (HSA) was investigated via fluorescence and circular dichroism spectroscopy. The results revealed that TBA-AlMo6-LA binds strongly to HSA (63% quenching at an HSA/TBA-AlMo6-LA ratio of 1:1), exhibiting static quenching. In contrast to TBA-AlMo6-LA, the nonfunctionalized polyoxometalate, Na3(H2O)6[Al(OH)6Mo6O18].2H2O (AlMo6), showed weak binding toward HSA (22% quenching at a HSA/AlMo6 ratio of 1:25). HSA binding was confirmed by X-ray structure analysis of the HSA-Myr-AlMo6-LA complex (Myr = myristate). These results provide a promising lead for the design of novel polyoxometalate-based hybrids that are able to exploit HSA as a delivery vehicle to improve their pharmacokinetics and bioactivity.

Binding of a Fatty Acid-Functionalized Anderson-Type Polyoxometalate to Human Serum Albumin.,Bijelic A, Dobrov A, Roller A, Rompel A Inorg Chem. 2020 Apr 7. doi: 10.1021/acs.inorgchem.9b03407. PMID:32255347^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S. An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7. PMID:8048949
↑ Rushbrook JI, Becker E, Schussler GC, Divino CM. Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7. PMID:7852505
↑ Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T. A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50. PMID:9329347
↑ Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S. Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54. PMID:9589637
↑ Lu J, Stewart AJ, Sadler PJ, Pinheiro TJ, Blindauer CA. Albumin as a zinc carrier: properties of its high-affinity zinc-binding site. Biochem Soc Trans. 2008 Dec;36(Pt 6):1317-21. doi: 10.1042/BST0361317. PMID:19021548 doi:10.1042/BST0361317
↑ Bijelic A, Dobrov A, Roller A, Rompel A. Binding of a Fatty Acid-Functionalized Anderson-Type Polyoxometalate to Human Serum Albumin. Inorg Chem. 2020 Apr 7. doi: 10.1021/acs.inorgchem.9b03407. PMID:32255347 doi:http://dx.doi.org/10.1021/acs.inorgchem.9b03407

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S. An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7. PMID:8048949

[2] Rushbrook JI, Becker E, Schussler GC, Divino CM. Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7. PMID:7852505

[3] Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T. A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50. PMID:9329347

[4] Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S. Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54. PMID:9589637

[5] Lu J, Stewart AJ, Sadler PJ, Pinheiro TJ, Blindauer CA. Albumin as a zinc carrier: properties of its high-affinity zinc-binding site. Biochem Soc Trans. 2008 Dec;36(Pt 6):1317-21. doi: 10.1042/BST0361317. PMID:19021548 doi:10.1042/BST0361317

[6] Bijelic A, Dobrov A, Roller A, Rompel A. Binding of a Fatty Acid-Functionalized Anderson-Type Polyoxometalate to Human Serum Albumin. Inorg Chem. 2020 Apr 7. doi: 10.1021/acs.inorgchem.9b03407. PMID:32255347 doi:http://dx.doi.org/10.1021/acs.inorgchem.9b03407

[1]

[2]

[3]

[4]

[5]

[6]