9ju1

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:34, 25 December 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 9ju1 is ON HOLD
+
==Helix-loop-helix peptide (VS42-LR3) in complex with VEGF-A==
 +
<StructureSection load='9ju1' size='340' side='right'caption='[[9ju1]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[9ju1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9JU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JU1 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]] 1.45&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=9ju1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ju1 OCA], [https://pdbe.org/9ju1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ju1 RCSB], [https://www.ebi.ac.uk/pdbsum/9ju1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ju1 ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[https://omim.org/entry/603933 603933]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Mid-sized binding peptides have recently emerged as a new therapeutic modality. A helix-loop-helix (HLH) peptide was designed as a scaffold for combinatorial peptide libraries. We screened the HLH peptide libraries against human vascular endothelial growth factor-A (VEGF) to generate a peptide, VS42-LR3, which inhibited VEGF/receptor interaction and suppressed tumor growth in a murine xenograft model of human colorectal cancer. Here, we report the first crystal structure of the HLH peptide in a complex with VEGF at high resolution using space-grown protein crystals. The X-ray structural analysis revealed that the monomeric VS42-LR3 adopted an HLH structure and bound to VEGF at the VEGF receptor-binding site. Interestingly, from the site-directed mutagenesis, thermodynamic analysis, and molecular dynamic simulations, it turned out that the loop region in the non-interacting surface to VEGF affected the structural rigidity of the whole HLH to increase the binding affinity. These findings provide valuable insights for the design of more structurally stable and higher affinity mid-sized binding peptides as well as HLH peptides, that could play a crucial role in advancing molecular-targeting therapies.
-
Authors: Kamo, M., Michigami, M., Inaka, K., Furubayashi, N., Kaito, S., Kobayashi, Y., Shinohara, Y., Fujii, I.
+
Structural insights into molecular-targeting helix-loop-helix peptide against vascular endothelial growth factor-A.,Michigami M, Notsu K, Kamo M, Hirokawa T, Kinoshita T, Inaka K, Nakase I, Fujii I Biochem Biophys Res Commun. 2024 Nov 19;734:150749. doi: , 10.1016/j.bbrc.2024.150749. Epub 2024 Sep 27. PMID:39357335<ref>PMID:39357335</ref>
-
Description: Helix-loop-helix peptide (VS42-LR3) in complex with VEGF-A
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Kamo, M]]
+
<div class="pdbe-citations 9ju1" style="background-color:#fffaf0;"></div>
-
[[Category: Kobayashi, Y]]
+
== References ==
-
[[Category: Kaito, S]]
+
<references/>
-
[[Category: Furubayashi, N]]
+
__TOC__
-
[[Category: Shinohara, Y]]
+
</StructureSection>
-
[[Category: Michigami, M]]
+
[[Category: Homo sapiens]]
-
[[Category: Fujii, I]]
+
[[Category: Large Structures]]
-
[[Category: Inaka, K]]
+
[[Category: Synthetic construct]]
 +
[[Category: Fujii I]]
 +
[[Category: Furubayashi N]]
 +
[[Category: Inaka K]]
 +
[[Category: Kaito S]]
 +
[[Category: Kamo M]]
 +
[[Category: Kobayashi Y]]
 +
[[Category: Michigami M]]
 +
[[Category: Shinohara Y]]

Current revision

Helix-loop-helix peptide (VS42-LR3) in complex with VEGF-A

PDB ID 9ju1

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9ju1"
Personal tools