1i22: Difference between revisions
New page: left|200px<br /> <applet load="1i22" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i22, resolution 1.80Å" /> '''MUTANT HUMAN LYSOZY... |
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[[Image:1i22.gif|left|200px]]<br /> | [[Image:1i22.gif|left|200px]]<br /><applet load="1i22" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1i22, resolution 1.80Å" /> | caption="1i22, resolution 1.80Å" /> | ||
'''MUTANT HUMAN LYSOZYME (A83K/Q86D/A92D)'''<br /> | '''MUTANT HUMAN LYSOZYME (A83K/Q86D/A92D)'''<br /> | ||
==Overview== | ==Overview== | ||
Structural determinants of Ca2+ binding sites within proteins typically | Structural determinants of Ca2+ binding sites within proteins typically comprise several acidic residues in appropriate juxtaposition. Three residues (Ala-83, Gln-86, and Ala-92) in human lysozyme are characteristically mutated to Lys, Asp, and Asp, respectively, in natural Ca2+ binding lysozymes and alpha-lactalbumins. The effects of these mutations on the stability and Ca2+ binding properties of human lysozyme were investigated using calorimetry and were interpreted with crystal structures. The double mutant, in which Glu-86 and Ala-92 were replaced with Asp, clearly showed Ca2+ binding affinity, whereas neither point mutant showed Ca2+ affinity, indicating that both residues are essential. The further mutation of Ala-83 --> Lys did not affect the Ca2+ binding of the double mutant. The point mutations Ala-83 --> Lys and Glu-86 --> Asp did not affect the stability, whereas the mutation Ala-92 --> Asp was about 1.3 kcal/mol less stable. Structural analyses showed that both Asp-86 and Lys-83 were exposed to solvent. Side chains of Asp-86 and Asp-91 were rotated in opposite directions about chi1 angle, as if to reduce the electrostatic repulsion. The charged amino acids at the Ca2+ binding site did not significantly affect stability of the protein, possibly because of the local conformational change of the side chains. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1I22 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] Full crystallographic information is available from [http:// | 1I22 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I22 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: mutant human lysozyme]] | [[Category: mutant human lysozyme]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:07:13 2008'' | ||
Revision as of 14:07, 21 February 2008
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MUTANT HUMAN LYSOZYME (A83K/Q86D/A92D)
OverviewOverview
Structural determinants of Ca2+ binding sites within proteins typically comprise several acidic residues in appropriate juxtaposition. Three residues (Ala-83, Gln-86, and Ala-92) in human lysozyme are characteristically mutated to Lys, Asp, and Asp, respectively, in natural Ca2+ binding lysozymes and alpha-lactalbumins. The effects of these mutations on the stability and Ca2+ binding properties of human lysozyme were investigated using calorimetry and were interpreted with crystal structures. The double mutant, in which Glu-86 and Ala-92 were replaced with Asp, clearly showed Ca2+ binding affinity, whereas neither point mutant showed Ca2+ affinity, indicating that both residues are essential. The further mutation of Ala-83 --> Lys did not affect the Ca2+ binding of the double mutant. The point mutations Ala-83 --> Lys and Glu-86 --> Asp did not affect the stability, whereas the mutation Ala-92 --> Asp was about 1.3 kcal/mol less stable. Structural analyses showed that both Asp-86 and Lys-83 were exposed to solvent. Side chains of Asp-86 and Asp-91 were rotated in opposite directions about chi1 angle, as if to reduce the electrostatic repulsion. The charged amino acids at the Ca2+ binding site did not significantly affect stability of the protein, possibly because of the local conformational change of the side chains.
DiseaseDisease
Known diseases associated with this structure: Amyloidosis, renal OMIM:[153450], Microphthalmia, syndromic 1 OMIM:[309800]
About this StructureAbout this Structure
1I22 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.
ReferenceReference
Structural and thermodynamic responses of mutations at a Ca2+ binding site engineered into human lysozyme., Kuroki R, Yutani K, J Biol Chem. 1998 Dec 18;273(51):34310-5. PMID:9852096
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