4pgj | pdb_00004pgj

Human heavy-chain domain antibody in complex with hen egg-white lysozyme

spinqualitylabelsall models 4pgj, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4pgj is a 4 chain structure with sequence from [1] and Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Activity: Lysozyme, with EC number 3.2.1.17 Resources: FirstGlance, OCA, RCSB, PDBsum Function [LYSC_CHICK] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus. Publication Abstract from PubMed Human VH single domains represent a promising class of antibody fragments with applications as therapeutic modalities. Unfortunately, isolated human VH domains also generally display poor biophysical properties and a propensity to aggregate. This has encouraged the development of non-human antibody domains as alternative means of antigen recognition and, in particular, camelid (VHH) domains. Naturally devoid of light chain partners, these domains are characterized by favourable biophysical properties and propensity for cleft binding, a highly desirable characteristic, allowing the targeting of cryptic epitopes. In contrast, previously reported structures of human VH single domains had failed to recapitulate this property. Here we report the engineering and characterization of phage display libraries of stable human VH domains, and the selection of binders against a diverse set of antigens. Unlike "camelized" human domains, the domains do not rely on potentially immunogenic framework mutations and maintain the structure of the VH/VL interface. Structure determination in complex with hen egg-white lysozyme revealed an extended VH binding interface, with complementarity determining region 3 (CDR3) deeply penetrating into the active site cleft, highly reminiscent to what has been observed for camelid domains. Taken together, our results demonstrate that fully human VH domains can be constructed that are not only stable and well-expressed, but also rival the cleft binding properties of camelid antibodies. Fully human VH single domains that rival the stability and cleft recognition of camelid antibodies.,Rouet R, Dudgeon K, Christie M, Langley D, Christ D J Biol Chem. 2015 Mar 3. pii: jbc.M114.614842. PMID:25737448 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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