8fsl: Difference between revisions
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==Human Mesothelin bound to a neutralizing VH domain antibody== | |||
<StructureSection load='8fsl' size='340' side='right'caption='[[8fsl]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8fsl]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Insect_expression_vector_pBlueBacmsGCA1His Insect expression vector pBlueBacmsGCA1His]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FSL 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]] 2.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=8fsl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fsl OCA], [https://pdbe.org/8fsl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fsl RCSB], [https://www.ebi.ac.uk/pdbsum/8fsl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fsl ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/MSLN_HUMAN MSLN_HUMAN] Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MSLN_HUMAN MSLN_HUMAN] Membrane-anchored forms may play a role in cellular adhesion.<ref>PMID:8288629</ref> <ref>PMID:14676194</ref> Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.<ref>PMID:8288629</ref> <ref>PMID:14676194</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mesothelin (MSLN) has been a validated tumor-associated antigen target for several solid tumors for over a decade, making it an attractive option for therapeutic interventions. Novel antibodies with high affinity and better therapeutic properties are needed. In the current study, we have isolated and characterized a novel heavy chain variable (VH) domain 3C9 from a large-size human immunoglobulin VH domain library. 3C9 exhibited high affinity (KD [dissociation constant] <3 nM) and binding specificity in a membrane proteome array (MPA). In a mouse xenograft model, 3C9 fused to human IgG1 Fc was detected at tumor sites as early as 8 h post-infusion and remained at the site for over 10 days. Furthermore, 3C9 fused to a human Fc domain drug conjugate effectively inhibited MSLN-positive tumor growth in a mouse xenograft model. The X-ray crystal structure of full-length MSLN in complex with 3C9 reveals interaction of the 3C9 domains with two distinctive residue patches on the MSLN surface. This newly discovered VH antibody domain has a high potential as a therapeutic candidate for MSLN-expressing cancers. | |||
Preclinical assessment of a novel human antibody VH domain targeting mesothelin as an antibody-drug conjugate.,Sun Z, Chu X, Adams C, Ilina TV, Guerrero M, Lin G, Chen C, Jelev D, Ishima R, Li W, Mellors JW, Calero G, Dimitrov DS Mol Ther Oncolytics. 2023 Sep 13;31:100726. doi: 10.1016/j.omto.2023.09.002. , eCollection 2023 Dec 19. PMID:37771390<ref>PMID:37771390</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Calero | <div class="pdbe-citations 8fsl" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Insect expression vector pBlueBacmsGCA1His]] | |||
[[Category: Large Structures]] | |||
[[Category: Calero G]] | |||
Latest revision as of 21:02, 29 May 2024
Human Mesothelin bound to a neutralizing VH domain antibodyHuman Mesothelin bound to a neutralizing VH domain antibody
Structural highlights
DiseaseMSLN_HUMAN Antibodies against MSLN are detected in patients with mesothelioma and ovarian cancer. FunctionMSLN_HUMAN Membrane-anchored forms may play a role in cellular adhesion.[1] [2] Megakaryocyte-potentiating factor (MPF) potentiates megakaryocyte colony formation in vitro.[3] [4] Publication Abstract from PubMedMesothelin (MSLN) has been a validated tumor-associated antigen target for several solid tumors for over a decade, making it an attractive option for therapeutic interventions. Novel antibodies with high affinity and better therapeutic properties are needed. In the current study, we have isolated and characterized a novel heavy chain variable (VH) domain 3C9 from a large-size human immunoglobulin VH domain library. 3C9 exhibited high affinity (KD [dissociation constant] <3 nM) and binding specificity in a membrane proteome array (MPA). In a mouse xenograft model, 3C9 fused to human IgG1 Fc was detected at tumor sites as early as 8 h post-infusion and remained at the site for over 10 days. Furthermore, 3C9 fused to a human Fc domain drug conjugate effectively inhibited MSLN-positive tumor growth in a mouse xenograft model. The X-ray crystal structure of full-length MSLN in complex with 3C9 reveals interaction of the 3C9 domains with two distinctive residue patches on the MSLN surface. This newly discovered VH antibody domain has a high potential as a therapeutic candidate for MSLN-expressing cancers. Preclinical assessment of a novel human antibody VH domain targeting mesothelin as an antibody-drug conjugate.,Sun Z, Chu X, Adams C, Ilina TV, Guerrero M, Lin G, Chen C, Jelev D, Ishima R, Li W, Mellors JW, Calero G, Dimitrov DS Mol Ther Oncolytics. 2023 Sep 13;31:100726. doi: 10.1016/j.omto.2023.09.002. , eCollection 2023 Dec 19. PMID:37771390[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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