7dha: Difference between revisions
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==== | ==crystal structure of CD38 in complex with daratumumab== | ||
<StructureSection load='7dha' size='340' side='right'caption='[[7dha]]' scene=''> | <StructureSection load='7dha' size='340' side='right'caption='[[7dha]], [[Resolution|resolution]] 2.55Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7dha]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHA FirstGlance]. <br> | ||
</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=7dha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dha OCA], [https://pdbe.org/7dha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dha RCSB], [https://www.ebi.ac.uk/pdbsum/7dha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dha ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55Å</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=7dha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dha OCA], [https://pdbe.org/7dha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dha RCSB], [https://www.ebi.ac.uk/pdbsum/7dha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dha ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CD38_HUMAN CD38_HUMAN] Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Multiple myeloma is a blood cancer characterized by the plasma cell malignancy in the bone marrow, resulting in the destruction of bone tissue. Recently, the US FDA approved two antibody drugs for the treatment of multiple myeloma, daratumumab and isatuximab, targeting CD38, a type II transmembrane glycoprotein highly expressed in plasma cells and multiple myeloma cells. Here, we report the crystal structure of CD38 in complex with the Fab fragment of daratumumab, providing its exact epitope on CD38 and the structural insights into the mechanism of action of the antibody drug. Daratumumab binds to a specific discontinuous region on CD38 that includes residues located opposite to the active site of CD38. All the six complementarity determining regions of daratumumab are involved in the CD38 interaction. The epitopes of daratumumab and isatuximab do not overlap at all and their bindings to CD38 induce different structural changes within the CD38 protein. This structural study can facilitate the design of improved biologics or effective combination therapies for the treatment of multiple myeloma. | |||
Crystal structure of CD38 in complex with daratumumab, a first-in-class anti-CD38 antibody drug for treating multiple myeloma.,Lee HT, Kim Y, Park UB, Jeong TJ, Lee SH, Heo YS Biochem Biophys Res Commun. 2021 Jan 15;536:26-31. doi: , 10.1016/j.bbrc.2020.12.048. Epub 2020 Dec 22. PMID:33360095<ref>PMID:33360095</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7dha" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Heo YS]] | ||
[[Category: Lee HT]] | |||
Latest revision as of 19:33, 29 November 2023
crystal structure of CD38 in complex with daratumumabcrystal structure of CD38 in complex with daratumumab
Structural highlights
FunctionCD38_HUMAN Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system. Publication Abstract from PubMedMultiple myeloma is a blood cancer characterized by the plasma cell malignancy in the bone marrow, resulting in the destruction of bone tissue. Recently, the US FDA approved two antibody drugs for the treatment of multiple myeloma, daratumumab and isatuximab, targeting CD38, a type II transmembrane glycoprotein highly expressed in plasma cells and multiple myeloma cells. Here, we report the crystal structure of CD38 in complex with the Fab fragment of daratumumab, providing its exact epitope on CD38 and the structural insights into the mechanism of action of the antibody drug. Daratumumab binds to a specific discontinuous region on CD38 that includes residues located opposite to the active site of CD38. All the six complementarity determining regions of daratumumab are involved in the CD38 interaction. The epitopes of daratumumab and isatuximab do not overlap at all and their bindings to CD38 induce different structural changes within the CD38 protein. This structural study can facilitate the design of improved biologics or effective combination therapies for the treatment of multiple myeloma. Crystal structure of CD38 in complex with daratumumab, a first-in-class anti-CD38 antibody drug for treating multiple myeloma.,Lee HT, Kim Y, Park UB, Jeong TJ, Lee SH, Heo YS Biochem Biophys Res Commun. 2021 Jan 15;536:26-31. doi: , 10.1016/j.bbrc.2020.12.048. Epub 2020 Dec 22. PMID:33360095[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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