4edx: Difference between revisions
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==Nerve Growth Factor in Complex with Fab from mouse mAb 911== | ==Nerve Growth Factor in Complex with Fab from mouse mAb 911== | ||
<StructureSection load='4edx' size='340' side='right' caption='[[4edx]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4edx' size='340' side='right'caption='[[4edx]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4edx]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4edx]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EDX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EDX FirstGlance]. <br> | ||
</td></tr> | </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=4edx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edx OCA], [https://pdbe.org/4edx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4edx RCSB], [https://www.ebi.ac.uk/pdbsum/4edx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4edx ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[[ | [[https://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN]] Defects in NGF are the cause of hereditary sensory and autonomic neuropathy type 5 (HSAN5) [MIM:[https://omim.org/entry/608654 608654]]. The hereditary sensory and autonomic neuropathies are a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable.<ref>PMID:14976160</ref> <ref>PMID:20978020</ref> <ref>PMID:22302274</ref> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN]] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: | [[Category: Eigenbrot C]] | ||
[[Category: | [[Category: Ultsch M]] | ||
Revision as of 10:06, 28 September 2022
Nerve Growth Factor in Complex with Fab from mouse mAb 911Nerve Growth Factor in Complex with Fab from mouse mAb 911
Structural highlights
Disease[NGF_HUMAN] Defects in NGF are the cause of hereditary sensory and autonomic neuropathy type 5 (HSAN5) [MIM:608654]. The hereditary sensory and autonomic neuropathies are a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable.[1] [2] [3] Function[NGF_HUMAN] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival. Publication Abstract from PubMedNerve growth factor (NGF) is indispensable during normal embryonic development and critical for the amplification of pain signals in adults. Intervention in NGF signaling holds promise for the alleviation of pain resulting from human diseases such as osteoarthritis, cancer and chronic lower back disorders. We developed a fast, high-fidelity method to convert a hybridoma-derived NGF-targeted mouse antibody into a clinical candidate. This method, termed Library Scanning Mutagenesis (LSM), resulted in the ultra-high affinity antibody tanezumab, a first-in-class anti-hyperalgesic specific for an NGF epitope. Functional and structural comparisons between tanezumab and the mouse 911 precursor antibody using neurotrophin-specific cell survival assays and X-ray crystal structures of both Fab-antigen complexes illustrated high fidelity retention of the NGF epitope. These results suggest the potential for wide applicability of the LSM method for optimization of well-characterized antibodies during humanization. Generation of a high-fidelity antibody against nerve growth factor using library scanning mutagenesis and validation with structures of the initial and optimized Fab-antigen complexes.,La Porte SL, Eigenbrot C, Ultsch M, Ho WH, Foletti D, Forgie A, Lindquist KC, Shelton DL, Pons J MAbs. 2014 Jul-Aug;6(4):1059-68. PMID:24830649[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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