1OL0

Crystal structure of a camelised human VH

Summary for 1OL0

• Entry DOI: 10.2210/pdb1ol0/pdb
• Related: 1A8J 1AJ7 1AR2 1B6D 1BM3 1BRE 1BWW 1CMO 1EK3 1EPF 1FIG 1IE5 1IGM 1IKF 1IND 1INE 1IVL 1JGL 1JVK 1KOA 1KSR 1LVE 1MCB 1MCC 1MCD 1MCE 1MCF 1MCH 1MCI 1MCJ 1MCK 1MCL 1MCN 1MCO 1MCP 1MCQ 1MCR 1MCS 1MCW 1REI 1VKX 1WIT 1WIU 2DL2 2DLI 2FB4 2IG2 2IMM 2IMN 2LOI 2MCG 2MCP 2RCS 3MCG 5LVE 7FAB 8FAB
• Descriptor: IMMUNOGLOBULIN G, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: immunoglobulin, camelised variable heavy domain
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 27449.56

Authors

Dottorini, T.,Vaughan, C.K.,Walsh, M.A.,Losurdo, P.,Sollazzo, M. (deposition date: 2003-08-02, release date: 2004-01-22, Last modification date: 2024-10-23)

Primary citation

Dottorini, T.,Vaughan, C.K.,Walsh, M.A.,Losurdo, P.,Sollazzo, M.
Crystal Structure of a Human Vh: Requirements for Maintaining a Monomeric Fragment
Biochemistry, 43:622-, 2004

PubMed Abstract: The variable domain of dromedary immunoglobulins comprises only the heavy chain and is missing the light-chain variable domain. This single domain is sufficient for antigen recognition and binding-half that required by other mammals. Human antibody-VHs have previously been camelized to be soluble stable fragments that retain antigen binding. Such engineered VHH are of interest in drug development, since they are nonimmunogenic, and in other biotechnology applications. We present the structure of a camelized human antibody fragment (cVH), which is a competitive and reversible inhibitor of the NS3 serine protease of the hepatitis C virus (HCV). In solution, this cVH undergoes a concentration-dependent monomer-dimer equilibrium. The structure confirms the minimum mutational requirements of the VL-binding face. The fragment also suggests a means by which the observed dimerization occurs, highlighting the importance of the composition of the CDR3 in maintaining a truly camelized VH.

PubMed: 14730966
DOI: 10.1021/BI035800B

Experimental method

X-RAY DIFFRACTION (1.8 Å)