About: Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

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About: Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms. The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms. (en)
Title	Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex (en)
skos:prefLabel	Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex (en)
skos:notation	RIV/61388963:_____/14:00435229!RIV15-GA0-61388963
http://linked.open...avai/riv/aktivita	I P
http://linked.open...avai/riv/aktivity	I, P(GBP208/12/G016), P(GPP207/11/P430)
http://linked.open...iv/cisloPeriodika	10
http://linked.open...vai/riv/dodaniDat	2015
http://linked.open...aciTvurceVysledku	Jiráček, Jiří Žáková, Lenka Lepšík, Martin Collinsová, Michaela Kletvíková, Emília
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ústav organické chemie a biochemie AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	19960
http://linked.open...ai/riv/idVysledku	RIV/61388963:_____/14:00435229
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	insulin; insulin receptor; complex; active form; analog; structure (en)
http://linked.open.../riv/klicoveSlovo	analog insulin structure insulin receptor complex active form
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[5BB5ADC1D00C]
http://linked.open...i/riv/nazevZdroje	Acta Crystallographica Section D-Biological Crystallography
http://linked.open...in/vavai/riv/obor	CE
http://linked.open...ichTvurcuVysledku	5 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...vavai/riv/projekt	Controlling structure and function of biomolecules at the molecular scale: theory meets experiment The role of T- and R-conformations of insulin in binding to the insulin receptor
http://linked.open...UplatneniVysledku	2014
http://linked.open...v/svazekPeriodika	70
http://linked.open...iv/tvurceVysledku	Lepšík, Martin Brzozowski, A. M. Jiráček, Jiří Turkenburg, J. P. Watson, C. J. Žáková, Lenka Kletvíková, Emília Collinsová, Michaela
http://linked.open...ain/vavai/riv/wos	000343060900025
issn	0907-4449
number of pages	10 (xsd:int)
http://bibframe.org/vocab/doi	10.1107/S1399004714017775

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