1f40

<StructureSection load='1f40' size='340' side='right'caption='[[1f40]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[1f40]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F40 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GPI:(2S)-[3-PYRIDYL-1-PROPYL]-1-[3,3-DIMETHYL-1,2-DIOXOPENTYL]-2-PYRROLIDINECARBOXYLATE'>GPI</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fkj|1fkj]], [[1fkg|1fkg]]</div></td></tr>

[[https://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN]] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref>

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== Publication Abstract from PubMed ==

The structure of a recently reported neurotrophic ligand, 3-(3-pyridyl)-1-propyl(2S)-1-(3,3-dimethyl-1, 2-dioxopentyl)-2-pyrrolidinecarboxylate, in complex with FKBP12 was determined using heteronuclear NMR spectroscopy. The inhibitor exhibits a binding mode analogous to that observed for the macrocycle FK506, used widely as an immunosuppressant, with the prolyl ring replacing the pipecolyl moiety and the amide bond in a trans conformation. However, fewer favourable protein-ligand interactions are detected in the structure of the complex, suggesting weaker binding compared with the immunosuppressant drug. Indeed, a micromolar dissociation constant was estimated from the NMR ligand titration profile, in contrast to the previously published nanomolar inhibition activity. Although the inhibitor possesses a remarkable structural simplicity with respect to FK506, 15N relaxation studies show that it induces similar effects on the protein dynamics, stabilizing the conformation of solvent-exposed residues which are important for mediating the interaction of immunophilin/ligand complexes with molecular targets and potentially for the transmission of the neurotrophic action of FKBP12 inhibitors.

Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics.,Sich C, Improta S, Cowley DJ, Guenet C, Merly JP, Teufel M, Saudek V Eur J Biochem. 2000 Sep;267(17):5342-55. PMID:10951192<ref>PMID:10951192</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1f40" style="background-color:#fffaf0;"></div>

[[Category: Human]]

[[Category: Cowley, D J]]

[[Category: Guenet, C]]

[[Category: Improta, S]]

[[Category: Merly, J P]]

[[Category: Saudek, V]]

[[Category: Sich, C]]

[[Category: Teufel, M]]

[[Category: Isomerase]]