1zdc: Difference between revisions

Latest revision as of 07:45, 30 October 2024

DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, 24 STRUCTURES

Structural highlights

1zdc is a 1 chain structure with sequence from Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 24 models
Ligands:	NH2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Starovasnik MA, Braisted AC, Wells JA. Structural mimicry of a native protein by a minimized binding domain. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10080-5. PMID:9294166

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OCA

[1] Starovasnik MA, Braisted AC, Wells JA. Structural mimicry of a native protein by a minimized binding domain. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10080-5. PMID:9294166

[1]

@@ Line 1: / Line 1: @@
-[[Image:1zdc.gif|left|200px]]<br /><applet load="1zdc" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1zdc" />
-'''DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, 24 STRUCTURES'''<br />
-==Overview==
+==DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, 24 STRUCTURES==
-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.
+<StructureSection load='1zdc' size='340' side='right'caption='[[1zdc]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1zdc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZDC FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 24 models</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zdc OCA], [https://pdbe.org/1zdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zdc RCSB], [https://www.ebi.ac.uk/pdbsum/1zdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zdc ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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==
+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<ref>PMID:9294166</ref>
-ZDC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZDC OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9294166 9294166]
+</div>
-[[Category: Protein complex]]
+<div class="pdbe-citations 1zdc" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Synthetic construct]]
-[[Category: Starovasnik, M.A.]]
+[[Category: Starovasnik MA]]
-[[Category: NH2]]
-[[Category: igg binding domain]]
-[[Category: protein a mimic]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 04:49:56 2007''

1zdc: Difference between revisions

Latest revision as of 07:45, 30 October 2024

DISULFIDE-STABILIZED MINI PROTEIN A DOMAIN, Z34C, NMR, 24 STRUCTURES

Structural highlights

Publication Abstract from PubMed

References

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