PDBsum entry: 1bzq

Hydrolase/immune system

PDB id: 1bzq

Contents

Protein chains

124 a.a. *

124 a.a. *

Ligands

PO4 ×4

* Residue conservation analysis

PDB id:

1bzq

Name:

Hydrolase/immune system

Title:

Complex of a dromedary single-domain vhh antibody fragment with rnase a

Structure:

Protein (rnase a). Chain: a, b, c, d. Protein (antibody cab-rn05). Chain: k, l, m, n. Fragment: variable domain. Engineered: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas. Other_details: rnase a supplied by sigma. Camelus dromedarius. Arabian camel. Organism_taxid: 9838. Cell: b-lymphocytes.

Biol. unit:

Octamer (from PQS)

Resolution:

2.80Å R-factor: 0.222 R-free: 0.282

Authors:

K.Decanniere,A.Desmyter,M.Gahroudhi,M.Lauwereys, S.Muyldermans,L.Wyns

Key ref:

K.Decanniere et al. (1999). A single-domain antibody fragment in complex with RNase A: non-canonical loop structures and nanomolar affinity using two CDR loops. Structure, 7, 361-370. PubMed id: 10196124 DOI: 10.1016/S0969-2126(99)80049-5

Date:

03-Nov-98 Release date: 11-Nov-98

Protein chains

P61823  (RNAS1_BOVIN) -  Ribonuclease pancreatic

Seq: 150 a.a.

Struc: 124 a.a.

Protein chain

No UniProt id for this chain

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.3.1.27.5 - Pancreatic ribonuclease.
• Reaction: Endonucleolytic cleavage to nucleoside 3'-phosphates and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biochemical function: nucleic acid binding (6 terms)

DOI no: 10.1016/S0969-2126(99)80049-5

Structure 7:361-370 (1999)

PubMed id: 10196124

A single-domain antibody fragment in complex with RNase A: non-canonical loop structures and nanomolar affinity using two CDR loops.

K.Decanniere, A.Desmyter, M.Lauwereys, M.A.Ghahroudi, S.Muyldermans, L.Wyns.

ABSTRACT

BACKGROUND: Camelid serum contains a large fraction of functional heavy-chain antibodies - homodimers of heavy chains without light chains. The variable domains of these heavy-chain antibodies (VHH) have a long complementarity determining region 3 (CDR3) loop that compensates for the absence of the antigen-binding loops of the variable light chains (VL). In the case of the VHH fragment cAb-Lys3, part of the 24 amino acid long CDR3 loop protrudes from the antigen-binding surface and inserts into the active-site cleft of its antigen, rendering cAb-Lys3 a competitive enzyme inhibitor. RESULTS: A dromedary VHH with specificity for bovine RNase A, cAb-RN05, has a short CDR3 loop of 12 amino acids and is not a competitive enzyme inhibitor. The structure of the cAb-RN05-RNase A complex has been solved at 2.8 A. The VHH scaffold architecture is close to that of a human VH (variable heavy chain). The structure of the antigen-binding hypervariable 1 loop (H1) of both cAb-RN05 and cAb-Lys3 differ from the known canonical structures; in addition these H1 loops resemble each other. The CDR3 provides an antigen-binding surface and shields the face of the domain that interacts with VL in conventional antibodies. CONCLUSIONS: VHHs adopt the common immunoglobulin fold of variable domains, but the antigen-binding loops deviate from the predicted canonical structure. We define a new canonical structure for the H1 loop of immunoglobulins, with cAb-RN05 and cAb-Lys3 as reference structures. This new loop structure might also occur in human or mouse VH domains. Surprisingly, only two loops are involved in antigen recognition; the CDR2 does not participate. Nevertheless, the antigen binding occurs with nanomolar affinities because of a preferential usage of mainchain atoms for antigen interaction.

Selected figure(s)

Figure 5.
Figure 5. Stereoview of the overlap of non-bulged torso CDR3 reference structure (PDB entry code 1flr [32], in blue) and the CDR3 of cAb-RN05 (yellow). Only the backbone atoms are shown for clarity. The hydrogen-bonding pattern of the reference structure is indicated by dotted lines. The position of amino acid residues 92, 97, 99 and 104 are indicated for reference. The figure was generated with SETOR [41].

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 361-370) copyright 1999.

Figure was selected by the author.