PDBsum entry 5a2k

Immune system

PDB id: 5a2k

Contents

Protein chain

225 a.a.

Ligands

ALA-PRO-ASP-THR-ARG-PRO

EDO ×6

A2G

Waters ×188

PDB id:

5a2k

Name:

Immune system

Title:

Crystal structure of scfv-sm3 in complex with apd-tgalnac-rp

Structure:

Ig lambda-1 chain v region s43. Chain: h. Fragment: residues 6-115,20-129. Synonym: scfv-sm3. Engineered: yes. Antigen tn, thr is covalently bound to galnac. Chain: p. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: komagataella pastoris. Expression_system_taxid: 4922. Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606

Resolution:

1.70Å R-factor: 0.177 R-free: 0.216

Authors:

N.Martinez-Saez,J.Castro-Lopez,J.Valero-Gonzalez,D.Madariaga, I.Companon,V.J.Somovilla,M.Salvado,J.L.Asensio,J.Jimenez-Barbero, A.Avenoza,J.H.Busto,G.J.L.Bernardes,J.M.Peregrina,R.Hurtado- Guerrero,F.Corzana

Key ref:

N.Martínez-Sáez et al. (2015). Deciphering the Non-Equivalence of Serine and Threonine O-Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody. Angew Chem Int Ed Engl, 54, 9830-9834. PubMed id: 26118689 DOI: 10.1002/anie.201502813

Date:

20-May-15 Release date: 03-Jun-15

Protein chain

P01727  (LV1E_MOUSE) -  Ig lambda-1 chain V region S43 from Mus musculus

Seq: 129 a.a.

Struc: 225 a.a.*

Protein chain

P01801  (HVM32_MOUSE) -  Ig heavy chain V-III region J606 from Mus musculus

Seq: 115 a.a.

Struc: 225 a.a.*

* PDB and UniProt seqs differ at 31 residue positions (black crosses)

DOI no: 10.1002/anie.201502813

Angew Chem Int Ed Engl 54:9830-9834 (2015)

PubMed id: 26118689

Deciphering the Non-Equivalence of Serine and Threonine O-Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody.

N.Martínez-Sáez, J.Castro-López, J.Valero-González, D.Madariaga, I.Compañón, V.J.Somovilla, M.Salvadó, J.L.Asensio, J.Jiménez-Barbero, A.Avenoza, J.H.Busto, G.J.Bernardes, J.M.Peregrina, R.Hurtado-Guerrero, F.Corzana.

ABSTRACT

The structural features of MUC1-like glycopeptides bearing the Tn antigen (α-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. For the α-O-GalNAc-Ser derivative, the glycosidic linkage adopts a high-energy conformation, barely populated in the free state. This unusual structure (also observed in an α-S-GalNAc-Cys mimic) is stabilized by hydrogen bonds between the peptidic fragment and the sugar. The selection of a particular peptide structure by the antibody is thus propagated to the carbohydrate through carbohydrate/peptide contacts, which force a change in the orientation of the sugar moiety. This seems to be unfeasible in the α-O-GalNAc-Thr glycopeptide owing to the more limited flexibility of the side chain imposed by the methyl group. Our data demonstrate the non-equivalence of Ser and Thr O-glycosylation points in molecular recognition processes. These features provide insight into the occurrence in nature of the APDTRP epitope for anti-MUC1 antibodies.