PDBsum entry 6pyd

Immune system

PDB id: 6pyd

Contents

Protein chains

210 a.a.

208 a.a.

Ligands

P4S ×2

Waters ×445

PDB id:

6pyd

Name:

Immune system

Title:

Structure of 3e9 antibody fab bound to marinobufagenin

Structure:

3e9 anti-marinobufagenin antibody fab heavy chain, recloned with human igg4 c region. Chain: h, a. Engineered: yes. 3e9 antibody fab light chain. Chain: l, b. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_taxid: 10029

Resolution:

2.00Å R-factor: 0.231 R-free: 0.276

Authors:

M.C.Franklin,L.E.Macdonald,J.Mcwhirter,A.J.Murphy

Key ref:

L.E.Macdonald et al. (2020). Kappa-on-Heavy (KoH) bodies are a distinct class of fully-human antibody-like therapeutic agents with antigen-binding properties. Proc Natl Acad Sci U S A, 117, 292-299. PubMed id: 31879340 DOI: 10.1073/pnas.1901734117

Date:

29-Jul-19 Release date: 25-Dec-19

Protein chains

No UniProt id for this chain

Struc: 210 a.a.

Protein chains

No UniProt id for this chain

Struc: 208 a.a.

DOI no: 10.1073/pnas.1901734117

Proc Natl Acad Sci U S A 117:292-299 (2020)

PubMed id: 31879340

Kappa-on-Heavy (KoH) bodies are a distinct class of fully-human antibody-like therapeutic agents with antigen-binding properties.

L.E.Macdonald, K.A.Meagher, M.C.Franklin, N.Levenkova, J.Hansen, A.T.Badithe, M.Zhong, P.Krueger, A.Rafique, N.Tu, J.Shevchuk, S.Wadhwa, G.Ehrlich, J.Bautista, C.Grant, L.Esau, W.T.Poueymirou, W.Auerbach, L.Morton, R.Babb, G.Chen, T.Huang, D.MacDonald, K.Graham, C.Gurer, V.A.Voronina, J.R.McWhirter, C.Guo, G.D.Yancopoulos, A.J.Murphy.

ABSTRACT

We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecules with an antigen binding site made up of 2 kappa variable domains. These molecules, named KoH bodies, structurally mimic naturally existing Bence-Jones light-chain dimers in their variable domains and remain wild-type in their antibody constant domains. Unlike artificially diversified, nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a configuration of normal Ig scaffolds that undergo natural diversification in B cells. Monoclonal KoH bodies have properties similar to those of conventional antibodies but exhibit an enhanced ability to bind small molecules such as the endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 Å further down into the combining site between the 2 variable domains.