6qio

From Proteopedia

(Difference between revisions)

Current revision

Ternary complex of FcRn ectodomain, FcRn binding optimised human serum albumin and the human growth hormone derivative somapacitan

Structural highlights

6qio is a 3 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 1.95Å
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

Somapacitan, a human growth hormone derivative that binds reversibly to albumin, was investigated for human serum albumin (HSA) and HSA domain binding. Isothermal titration calorimetry (ITC) binding profiles showed high-affinity binding ( approximately 100-1000 nM) of one somapacitan molecule and low-affinity binding ( approximately 1000-10000 nM) of one to two somapacitan molecules to HSA. The high-affinity site was identified in HSA domain III using size exclusion chromatography (SEC) and ITC. SEC studies showed that the neonatal Fc receptor shields one binding site for somapacitan, indicating its position in domain III. A crystal structure of somapacitan in complex with HSA optimized for neonatal Fc receptor binding, having four amino acid residue replacements, identified a low-affinity site in fatty acid-binding site 6 (domain II). Surface plasmon resonance (SPR) showed these replacements affect the kinetics of the high-affinity binding site. Furthermore, small-angle X-ray scattering and SPR brace two somapacitan-binding sites on HSA.

Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative.,Johansson E, Nielsen AD, Demuth H, Wiberg C, Schjodt CB, Huang T, Chen J, Jensen S, Petersen J, Thygesen P Biochemistry. 2020 Apr 14;59(14):1410-1419. doi: 10.1021/acs.biochem.0c00019., Epub 2020 Mar 30. PMID:32208682^[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
↑ Johansson E, Nielsen AD, Demuth H, Wiberg C, Schjodt CB, Huang T, Chen J, Jensen S, Petersen J, Thygesen P. Identification of Binding Sites on Human Serum Albumin for Somapacitan, a Long-Acting Growth Hormone Derivative. Biochemistry. 2020 Apr 14;59(14):1410-1419. doi: 10.1021/acs.biochem.0c00019., Epub 2020 Mar 30. PMID:32208682 doi:http://dx.doi.org/10.1021/acs.biochem.0c00019

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6qio"

Categories: Homo sapiens | Large Structures | Johansson E

@@ Line 3: / Line 3: @@
 <StructureSection load='6qio' size='340' side='right'caption='[[6qio]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6qio]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QIO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6qio]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QIO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QIO FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=JG5:(2S)-6-acetamido-2-[[2-[2-[2-[[4-carboxy-4-[[(4S)-4-carboxy-4-[[2-[2-[2-[4-[16-(1H-tetrazol-5-yl)hexadecanoylsulfamoyl]butanoylamino]ethoxy]ethoxy]acetyl]amino]butanoyl]amino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]hexanoic+acid'>JG5</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=JG5:(2~{S})-6-acetamido-2-[2-[2-[2-[[(4~{R})-5-oxidanyl-5-oxidanylidene-4-[[(4~{S})-5-oxidanyl-5-oxidanylidene-4-[2-[2-[2-[4-[16-(2~{H}-1,2,3,4-tetrazol-5-yl)hexadecanoylsulfamoyl]butanoylamino]ethoxy]ethoxy]ethanoylamino]pentanoyl]amino]pentanoyl]amino]ethoxy]ethoxy]ethanoylamino]hexanoic+acid'>JG5</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6qio FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qio OCA], [https://pdbe.org/6qio PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qio RCSB], [https://www.ebi.ac.uk/pdbsum/6qio PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qio ProSAT]</span></td></tr>
 </table>

6qio

From Proteopedia

Current revision

Ternary complex of FcRn ectodomain, FcRn binding optimised human serum albumin and the human growth hormone derivative somapacitan

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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