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| [[Image:1l24.jpg|left|200px]] | | {{Seed}} |
| | [[Image:1l24.png|left|200px]] |
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| {{STRUCTURE_1l24| PDB=1l24 | SCENE= }} | | {{STRUCTURE_1l24| PDB=1l24 | SCENE= }} |
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| '''ENHANCED PROTEIN THERMOSTABILITY FROM SITE-DIRECTED MUTATIONS THAT DECREASE THE ENTROPY OF UNFOLDING'''
| | ===ENHANCED PROTEIN THERMOSTABILITY FROM SITE-DIRECTED MUTATIONS THAT DECREASE THE ENTROPY OF UNFOLDING=== |
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| ==Overview==
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| It is proposed that the stability of a protein can be increased by selected amino acid substitutions that decrease the configurational entropy of unfolding. Two such substitutions, one of the form Xaa----Pro and the other of the form Gly----Xaa, were constructed in bacteriophage T4 lysozyme at sites consistent with the known three-dimensional structure. Both substitutions stabilize the protein toward reversible and irreversible thermal denaturation at physiological pH. The substitutions have no effect on enzymatic activity. High-resolution crystallographic analysis of the proline-containing mutant protein (Ala-82----Pro) shows that its three-dimensional structure is essentially identical with the wild-type enzyme. The overall structure of the other mutant enzyme (Gly-77----Ala) is also very similar to wild-type lysozyme, although there are localized conformational adjustments in the vicinity of the altered amino acid. The combination of a number of such amino acid replacements, each of which is expected to contribute approximately 1 kcal/mol (1 cal = 4.184 J) to the free energy of folding, may provide a general strategy for substantial improvement in the stability of a protein.
| | The line below this paragraph, {{ABSTRACT_PUBMED_3477797}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 3477797 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_3477797}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Matthews, B W.]] | | [[Category: Matthews, B W.]] |
| [[Category: Nicholson, H.]] | | [[Category: Nicholson, H.]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:27:12 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:31:45 2008'' |
