1zsz
From Proteopedia
(New page: 200px<br /><applet load="1zsz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zsz, resolution 2.00Å" /> '''Crystal structure of...) |
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| - | [[Image:1zsz.gif|left|200px]]<br /><applet load="1zsz" size=" | + | [[Image:1zsz.gif|left|200px]]<br /><applet load="1zsz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1zsz, resolution 2.00Å" /> | caption="1zsz, resolution 2.00Å" /> | ||
'''Crystal structure of a computationally designed SspB heterodimer'''<br /> | '''Crystal structure of a computationally designed SspB heterodimer'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein-protein interactions can be designed computationally by using | + | Protein-protein interactions can be designed computationally by using positive strategies that maximize the stability of the desired structure and/or by negative strategies that seek to destabilize competing states. Here, we compare the efficacy of these methods in reengineering a protein homodimer into a heterodimer. The stability-design protein (positive design only) was experimentally more stable than the specificity-design heterodimer (positive and negative design). By contrast, only the specificity-design protein assembled as a homogenous heterodimer in solution, whereas the stability-design protein formed a mixture of homodimer and heterodimer species. The experimental stabilities of the engineered proteins correlated roughly with their calculated stabilities, and the crystal structure of the specificity-design heterodimer showed most of the predicted side-chain packing interactions and a main-chain conformation indistinguishable from the wild-type structure. These results indicate that the design simulations capture important features of both stability and structure and demonstrate that negative design can be critical for attaining specificity when competing states are close in structure space. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZSZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1ZSZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Haemophilus_influenzae Haemophilus influenzae] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZSZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Haemophilus influenzae]] | [[Category: Haemophilus influenzae]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Baker, T | + | [[Category: Baker, T A.]] |
| - | [[Category: Bolon, D | + | [[Category: Bolon, D N.]] |
| - | [[Category: Grant, R | + | [[Category: Grant, R A.]] |
| - | [[Category: Sauer, R | + | [[Category: Sauer, R T.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: aaa]] | [[Category: aaa]] | ||
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[[Category: specificity]] | [[Category: specificity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:18:46 2008'' |
Revision as of 14:18, 21 February 2008
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Crystal structure of a computationally designed SspB heterodimer
Overview
Protein-protein interactions can be designed computationally by using positive strategies that maximize the stability of the desired structure and/or by negative strategies that seek to destabilize competing states. Here, we compare the efficacy of these methods in reengineering a protein homodimer into a heterodimer. The stability-design protein (positive design only) was experimentally more stable than the specificity-design heterodimer (positive and negative design). By contrast, only the specificity-design protein assembled as a homogenous heterodimer in solution, whereas the stability-design protein formed a mixture of homodimer and heterodimer species. The experimental stabilities of the engineered proteins correlated roughly with their calculated stabilities, and the crystal structure of the specificity-design heterodimer showed most of the predicted side-chain packing interactions and a main-chain conformation indistinguishable from the wild-type structure. These results indicate that the design simulations capture important features of both stability and structure and demonstrate that negative design can be critical for attaining specificity when competing states are close in structure space.
About this Structure
1ZSZ is a Protein complex structure of sequences from Haemophilus influenzae with as ligand. Full crystallographic information is available from OCA.
Reference
Specificity versus stability in computational protein design., Bolon DN, Grant RA, Baker TA, Sauer RT, Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12724-9. Epub 2005 Aug 29. PMID:16129838
Page seeded by OCA on Thu Feb 21 16:18:46 2008
Categories: Haemophilus influenzae | Protein complex | Baker, T A. | Bolon, D N. | Grant, R A. | Sauer, R T. | MG | Aaa | Adaptor | Protein design | Specificity
