From Proteopedia
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| | {{STRUCTURE_1zdd| PDB=1zdd | SCENE= }} | | {{STRUCTURE_1zdd| PDB=1zdd | SCENE= }} |
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| - | '''DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, MINIMIZED MEAN STRUCTURE'''
| + | ===DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, MINIMIZED MEAN STRUCTURE=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_9294166}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9294166 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9294166}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDD OCA]. | + | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDD OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Igg binding domain]] | | [[Category: Igg binding domain]] |
| | [[Category: Protein a mimic]] | | [[Category: Protein a mimic]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:29:31 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 10:07:34 2008'' |
Revision as of 07:07, 29 July 2008
Template:STRUCTURE 1zdd
DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, MINIMIZED MEAN STRUCTURE
Template:ABSTRACT PUBMED 9294166
About this Structure
Full experimental 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
Page seeded by OCA on Tue Jul 29 10:07:34 2008
