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1zdc
From Proteopedia
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DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, 24 STRUCTURES
Overview
The affinity between molecules depends both on the nature and presentation, of the contacts. Here, we observe coupling of functional and structural, elements when a protein binding domain is evolved to a smaller functional, mimic. Previously, a 38-residue form of the 59-residue B-domain of protein, A, termed Z38, was selected by phage display. Z38 contains 13 mutations, and binds IgG only 10-fold weaker than the native B-domain. We present the, solution structure of Z38 and show that it adopts a tertiary structure, remarkably similar to that observed for the first two helices of B-domain, in the B-domain/Fc complex [Deisenhofer, J. (1981) Biochemistry 20, 2361-2370], although it is significantly less stable. Based on this, structure, we have improved on Z38 by designing a 34-residue, disulfide-bonded variant (Z34C) that has dramatically enhanced stability, and binds IgG with 9-fold higher affinity. The improved stability of Z34C, led to NMR spectra with much greater chemical shift dispersion, resulting, in a more precisely determined structure. Z34C, like Z38, has a structure, virtually identical to the equivalent region from native protein A, domains. The well-defined hydrophobic core of Z34C reveals key structural, features that have evolved in this small, functional domain. Thus, the, stabilized two-helix peptide, about half the size and having one-third of, the remaining residues altered, accurately mimics both the structure and, function of the native domain.
About this Structure
1ZDC is a Protein complex structure of sequences from Synthetic construct with NH2 as ligand. Full crystallographic information is available from OCA.
Reference
Structural mimicry of a native protein by a minimized binding domain., Starovasnik MA, Braisted AC, Wells JA, Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10080-5. PMID:9294166
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