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5b8c

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Revision as of 08:48, 11 March 2020

High resolution structure of the human PD-1 in complex with pembrolizumab Fv

Structural highlights

5b8c is a 12 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PDCD1_HUMAN] Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM:605218]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.^[1]

Function

[PDCD1_HUMAN] Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors.^[2]

Publication Abstract from PubMed

Pembrolizumab is an FDA-approved therapeutic antibody that targets the programmed cell death-1 (PD-1) to block the immune checkpoint pathway for the treatment of various types of cancer. It receives remarkable attention due to the high degree of efficacy. Very recently, the crystal structure of the Fab fragment of pembrolizumab (PemFab) in complex with the extracellular domain of human PD-1 (PD-1ECD) was reported at a resolution of 2.9 A. However, this relatively low-resolution structural data fails to provide sufficient information on interfacial water molecules at the binding interface that substantially contribute to affinity and specificity between the therapeutic antibody and target. Here, we present the independently determined crystal structure of the Fv fragment of pembrolizumab (PemFv) in complex with the PD-1ECD at a resolution of 2.15 A. This high-resolution structure allows the accurate mapping of the interaction including water-mediated hydrogen bonds and provides, for the first time, a coherent explanation of PD-1 antagonism by pembrolizumab. Our structural data also provides new insights into the rational design of improved anti-PD-1 therapeutics.

High-resolution crystal structure of the therapeutic antibody pembrolizumab bound to the human PD-1.,Horita S, Nomura Y, Sato Y, Shimamura T, Iwata S, Nomura N Sci Rep. 2016 Oct 13;6:35297. doi: 10.1038/srep35297. PMID:27734966^[3]

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

References

↑ Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdottir H, Grondal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jonssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcon-Segovia D, Steinsson K, Alarcon-Riquelme ME. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet. 2002 Dec;32(4):666-9. Epub 2002 Oct 28. PMID:12402038 doi:10.1038/ng1020
↑ Fife BT, Pauken KE. The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Ann N Y Acad Sci. 2011 Jan;1217:45-59. doi: 10.1111/j.1749-6632.2010.05919.x. PMID:21276005 doi:10.1111/j.1749-6632.2010.05919.x
↑ Horita S, Nomura Y, Sato Y, Shimamura T, Iwata S, Nomura N. High-resolution crystal structure of the therapeutic antibody pembrolizumab bound to the human PD-1. Sci Rep. 2016 Oct 13;6:35297. doi: 10.1038/srep35297. PMID:27734966 doi:http://dx.doi.org/10.1038/srep35297

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5b8c"

@@ Line 1: / Line 1: @@
 ==High resolution structure of the human PD-1 in complex with pembrolizumab Fv==
-<StructureSection load='5b8c' size='340' side='right' caption='[[5b8c]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
+<StructureSection load='5b8c' size='340' side='right'caption='[[5b8c]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5b8c]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B8C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B8C FirstGlance]. <br>
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5b8c" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cell death protein|Cell death protein]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Horita, S]]
 [[Category: Iwata, S]]

5b8c

From Proteopedia

Revision as of 08:48, 11 March 2020

High resolution structure of the human PD-1 in complex with pembrolizumab Fv

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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