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5udd

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Current revision

Crystal Structure of RSV F B9320 Bound to MEDI8897

Structural highlights

5udd is a 21 chain structure with sequence from Homo sapiens and Human Respiratory syncytial virus 9320. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 4.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q6V2E7_HRSV

Publication Abstract from PubMed

Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose. MEDI8897*, a highly potent human antibody, was optimized from antibody D25, which targets the prefusion conformation of the RSV fusion (F) protein. Crystallographic analysis of Fab in complex with RSV F from subtypes A and B reveals that MEDI8897* binds a highly conserved epitope. MEDI8897* neutralizes a diverse panel of RSV A and B strains with >50-fold higher activity than palivizumab. At similar serum concentrations, prophylactic administration of MEDI8897* was ninefold more potent than palivizumab at reducing pulmonary viral loads by >3 logs in cotton rats infected with either RSV A or B subtypes. MEDI8897 was generated by the introduction of triple amino acid substitutions (YTE) into the Fc domain of MEDI8897*, which led to more than threefold increased half-life in cynomolgus monkeys compared to non-YTE antibody. Considering the pharmacokinetics of palivizumab in infants, which necessitates five monthly doses for protection during an RSV season, the high potency and extended half-life of MEDI8897 support its development as a cost-effective option to protect all infants from RSV disease with once-per-RSV-season dosing in the clinic.

A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants.,Zhu Q, McLellan JS, Kallewaard NL, Ulbrandt ND, Palaszynski S, Zhang J, Moldt B, Khan A, Svabek C, McAuliffe JM, Wrapp D, Patel NK, Cook KE, Richter BWM, Ryan PC, Yuan AQ, Suzich JA Sci Transl Med. 2017 May 3;9(388). pii: eaaj1928. doi:, 10.1126/scitranslmed.aaj1928. PMID:28469033^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhu Q, McLellan JS, Kallewaard NL, Ulbrandt ND, Palaszynski S, Zhang J, Moldt B, Khan A, Svabek C, McAuliffe JM, Wrapp D, Patel NK, Cook KE, Richter BWM, Ryan PC, Yuan AQ, Suzich JA. A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci Transl Med. 2017 May 3;9(388). pii: eaaj1928. doi:, 10.1126/scitranslmed.aaj1928. PMID:28469033 doi:http://dx.doi.org/10.1126/scitranslmed.aaj1928

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5udd"

Categories: Homo sapiens | Human Respiratory syncytial virus 9320 | Large Structures | McLellan JS

@@ Line 3: / Line 3: @@
 <StructureSection load='5udd' size='340' side='right'caption='[[5udd]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5udd]] is a 21 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus_9320 Human respiratory syncytial virus 9320]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UDD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UDD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5udd]] is a 21 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_Respiratory_syncytial_virus_9320 Human Respiratory syncytial virus 9320]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UDD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UDD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 4.3&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5udc|5udc]], [[5ude|5ude]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://proteopedia.org/fgij/fg.htm?mol=5udd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5udd OCA], [http://pdbe.org/5udd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5udd RCSB], [http://www.ebi.ac.uk/pdbsum/5udd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5udd ProSAT]</span></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=5udd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5udd OCA], [https://pdbe.org/5udd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5udd RCSB], [https://www.ebi.ac.uk/pdbsum/5udd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5udd ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q6V2E7_HRSV Q6V2E7_HRSV]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Human respiratory syncytial virus 9320]]
+[[Category: Human Respiratory syncytial virus 9320]]
 [[Category: Large Structures]]
-[[Category: McLellan, J S]]
+[[Category: McLellan JS]]
-[[Category: Antibody]]
-[[Category: Fusion glycoprotein]]
-[[Category: Immune system]]
-[[Category: Viral protein-immune system complex]]
-[[Category: Virus]]

5udd

From Proteopedia

Current revision

Crystal Structure of RSV F B9320 Bound to MEDI8897

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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