Sandbox454: Difference between revisions

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== PemFv/PD-1 Interaction ==

The Fv fragment of pembrolizumab (PemFv) can form a complex with the extracellular domain (ECD) of PD-1. Both PemFv and PD-1ECD contain interchain disulfide bonds. PemFv interacts predominantly in the major groove of PD-1, which is formed on one surface by the CC’FG antiparallel β−sheet and the BC, C’D, and FG loops. There are 15 direct hydrogen bonds between the residues, 15 water-mediated hydrogen bonds, 2 salt bridges, and many hydrophobic interactions. A very large solvent-accessible surface area of 1,137Å2 is buried on PD-1ECD due to the convoluted interaction. There are a total of 26 PD-1ECD residues involved in the interaction with PemFv, with residues in loop C’D (Pro84 to Gly90) and strand C’ (Gln75 to Lys 78) playing a major role. These key components of PD-1 mainly form interactions through salt bridges and hydrogen bonds with CRD-L3, CDR-H1, CDR-H2, CDR-H3 of pembrolizumab. It is beleived that the sugar chains of PD-1 have no ~~phsyical~~ contact with pembrolizumab due to the N-linked glycosylated residues (Asn49, Asn58, Asn74, and Asn116) being located away from the interaface <ref name="horita" />.

The Fv fragment of pembrolizumab (PemFv) can form a complex with the extracellular domain (ECD) of PD-1. Both PemFv and PD-1ECD contain interchain disulfide bonds. PemFv interacts predominantly in the major groove of PD-1, which is formed on one surface by the CC’FG antiparallel β−sheet and the BC, C’D, and FG loops. There are 15 direct hydrogen bonds between the residues, 15 water-mediated hydrogen bonds, 2 salt bridges, and many hydrophobic interactions. A very large solvent-accessible surface area of 1,137Å2 is buried on PD-1ECD due to the convoluted interaction. There are a total of 26 PD-1ECD residues involved in the interaction with PemFv, with residues in loop C’D (Pro84 to Gly90) and strand C’ (Gln75 to Lys 78) playing a major role. These key components of PD-1 mainly form interactions through salt bridges and hydrogen bonds with CRD-L3, CDR-H1, CDR-H2, CDR-H3 of pembrolizumab. It is beleived that the sugar chains of PD-1 have no physical contact with pembrolizumab due to the N-linked glycosylated residues (Asn49, Asn58, Asn74, and Asn116) being located away from the interaface <ref name="horita" />.

== PD-L1/PD-1 Interaction ==

Sandbox454: Difference between revisions

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 == PemFv/PD-1 Interaction ==
-The Fv fragment of pembrolizumab (PemFv) can form a complex with the extracellular domain (ECD) of PD-1. Both PemFv and PD-1ECD contain interchain disulfide bonds. PemFv interacts predominantly in the major groove of PD-1, which is formed on one surface by the CC’FG antiparallel β−sheet and the BC, C’D, and FG loops. There are 15 direct hydrogen bonds between the residues, 15 water-mediated hydrogen bonds, 2 salt bridges, and many hydrophobic interactions. A very large solvent-accessible surface area of 1,137Å2 is buried on PD-1ECD due to the convoluted interaction. There are a total of 26 PD-1ECD residues involved in the interaction with PemFv, with residues in loop C’D (Pro84 to Gly90) and strand C’ (Gln75 to Lys 78) playing a major role. These key components of PD-1 mainly form interactions through salt bridges and hydrogen bonds with CRD-L3, CDR-H1, CDR-H2, CDR-H3 of pembrolizumab. It is beleived that the sugar chains of PD-1 have no phsyical contact with pembrolizumab due to the N-linked glycosylated residues (Asn49, Asn58, Asn74, and Asn116) being located away from the interaface <ref name="horita" />.
+The Fv fragment of pembrolizumab (PemFv) can form a complex with the extracellular domain (ECD) of PD-1. Both PemFv and PD-1ECD contain interchain disulfide bonds. PemFv interacts predominantly in the major groove of PD-1, which is formed on one surface by the CC’FG antiparallel β−sheet and the BC, C’D, and FG loops. There are 15 direct hydrogen bonds between the residues, 15 water-mediated hydrogen bonds, 2 salt bridges, and many hydrophobic interactions. A very large solvent-accessible surface area of 1,137Å2 is buried on PD-1ECD due to the convoluted interaction. There are a total of 26 PD-1ECD residues involved in the interaction with PemFv, with residues in loop C’D (Pro84 to Gly90) and strand C’ (Gln75 to Lys 78) playing a major role. These key components of PD-1 mainly form interactions through salt bridges and hydrogen bonds with CRD-L3, CDR-H1, CDR-H2, CDR-H3 of pembrolizumab. It is beleived that the sugar chains of PD-1 have no physical contact with pembrolizumab due to the N-linked glycosylated residues (Asn49, Asn58, Asn74, and Asn116) being located away from the interaface <ref name="horita" />.
 == PD-L1/PD-1 Interaction ==