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| - | [[Image:1ioc.gif|left|200px]] | |
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| - | {{Structure
| + | ==CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME, EAEA-I56T== |
| - | |PDB= 1ioc |SIZE=350|CAPTION= <scene name='initialview01'>1ioc</scene>, resolution 2.4Å
| + | <StructureSection load='1ioc' size='340' side='right'caption='[[1ioc]], [[Resolution|resolution]] 2.40Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>
| + | <table><tr><td colspan='2'>[[1ioc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IOC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IOC FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[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] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ioc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ioc OCA], [https://pdbe.org/1ioc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ioc RCSB], [https://www.ebi.ac.uk/pdbsum/1ioc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ioc ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[1c7p|1C7P]] | + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ioc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ioc OCA], [http://www.ebi.ac.uk/pdbsum/1ioc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ioc RCSB]</span> | + | == Disease == |
| - | }}
| + | [https://www.uniprot.org/uniprot/LYSC_HUMAN LYSC_HUMAN] Defects in LYZ are a cause of amyloidosis type 8 (AMYL8) [MIM:[https://omim.org/entry/105200 105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.<ref>PMID:8464497</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LYSC_HUMAN LYSC_HUMAN] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/io/1ioc_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ioc ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | To understand the mechanism of amyloid fibril formation of a protein, we examined wild-type and three mutant human lysozymes containing both amyloidogenic and non-amyloidogenic proteins: I56T (amyloidogenic); EAEA, which has four additional residues (Glu-Ala-Glu-Ala-) at the N-terminus located on a beta-structure; and EAEA-I56T, which is an I56T mutant of EAEA. All formed amyloid-like fibrils through an in the increase contents of alpha-helix with increasing concentration of ethanol. The order of propensity for amyloid-like fibril formation in highly concentrated ethanol solution is EAEA-I56T > EAEA > I56T > wild-type. This order is almost the reverse of the order of conformational stability of these proteins, wild-type > EAEA > I56T > EAEA-I56T. The important views in this work are as follows. (i) Artificially modified proteins formed amyloid fibrils in vitro. This means that amyloid formation is a generic property of polypeptide chains. (ii) The amyloidogenic mutation Ile56 to Thr caused the destabilization and promoted fibril formation in the wild-type and EAEA human lysozymes, indicating that instability facilitates amyloid formation. (iii) The mutant protein EAEA human lysozyme had higher propensity for fibril formation than the amyloidogenic mutant protein, indicating that amyloid formation is controlled not only by stability but also by other factors. In this case, appending polypeptide chains to a beta-structure accelerated amyloid formation. |
| | | | |
| - | '''CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME, EAEA-I56T'''
| + | Elongation in a beta-structure promotes amyloid-like fibril formation of human lysozyme.,Goda S, Takano K, Yamagata Y, Maki S, Namba K, Yutani K J Biochem. 2002 Oct;132(4):655-61. PMID:12359083<ref>PMID:12359083</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 1ioc" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | To understand the mechanism of amyloid fibril formation of a protein, we examined wild-type and three mutant human lysozymes containing both amyloidogenic and non-amyloidogenic proteins: I56T (amyloidogenic); EAEA, which has four additional residues (Glu-Ala-Glu-Ala-) at the N-terminus located on a beta-structure; and EAEA-I56T, which is an I56T mutant of EAEA. All formed amyloid-like fibrils through an in the increase contents of alpha-helix with increasing concentration of ethanol. The order of propensity for amyloid-like fibril formation in highly concentrated ethanol solution is EAEA-I56T > EAEA > I56T > wild-type. This order is almost the reverse of the order of conformational stability of these proteins, wild-type > EAEA > I56T > EAEA-I56T. The important views in this work are as follows. (i) Artificially modified proteins formed amyloid fibrils in vitro. This means that amyloid formation is a generic property of polypeptide chains. (ii) The amyloidogenic mutation Ile56 to Thr caused the destabilization and promoted fibril formation in the wild-type and EAEA human lysozymes, indicating that instability facilitates amyloid formation. (iii) The mutant protein EAEA human lysozyme had higher propensity for fibril formation than the amyloidogenic mutant protein, indicating that amyloid formation is controlled not only by stability but also by other factors. In this case, appending polypeptide chains to a beta-structure accelerated amyloid formation.
| + | *[[Lysozyme 3D structures|Lysozyme 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 1IOC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IOC OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | Elongation in a beta-structure promotes amyloid-like fibril formation of human lysozyme., Goda S, Takano K, Yamagata Y, Maki S, Namba K, Yutani K, J Biochem. 2002 Oct;132(4):655-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12359083 12359083]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Lysozyme]] | + | [[Category: Large Structures]] |
| - | [[Category: Single protein]]
| + | [[Category: Goda S]] |
| - | [[Category: Goda, S.]] | + | [[Category: Takano K]] |
| - | [[Category: Takano, K.]] | + | [[Category: Yamagata Y]] |
| - | [[Category: Yamagata, Y.]] | + | [[Category: Yutani K]] |
| - | [[Category: Yutani, K.]] | + | |
| - | [[Category: amyloid]]
| + | |
| - | [[Category: human lysozyme]]
| + | |
| - | [[Category: mutant]]
| + | |
| - | [[Category: stability]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:22:28 2008''
| + | |
| Structural highlights
Disease
LYSC_HUMAN Defects in LYZ are a cause of amyloidosis type 8 (AMYL8) [MIM:105200; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.[1]
Function
LYSC_HUMAN Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
To understand the mechanism of amyloid fibril formation of a protein, we examined wild-type and three mutant human lysozymes containing both amyloidogenic and non-amyloidogenic proteins: I56T (amyloidogenic); EAEA, which has four additional residues (Glu-Ala-Glu-Ala-) at the N-terminus located on a beta-structure; and EAEA-I56T, which is an I56T mutant of EAEA. All formed amyloid-like fibrils through an in the increase contents of alpha-helix with increasing concentration of ethanol. The order of propensity for amyloid-like fibril formation in highly concentrated ethanol solution is EAEA-I56T > EAEA > I56T > wild-type. This order is almost the reverse of the order of conformational stability of these proteins, wild-type > EAEA > I56T > EAEA-I56T. The important views in this work are as follows. (i) Artificially modified proteins formed amyloid fibrils in vitro. This means that amyloid formation is a generic property of polypeptide chains. (ii) The amyloidogenic mutation Ile56 to Thr caused the destabilization and promoted fibril formation in the wild-type and EAEA human lysozymes, indicating that instability facilitates amyloid formation. (iii) The mutant protein EAEA human lysozyme had higher propensity for fibril formation than the amyloidogenic mutant protein, indicating that amyloid formation is controlled not only by stability but also by other factors. In this case, appending polypeptide chains to a beta-structure accelerated amyloid formation.
Elongation in a beta-structure promotes amyloid-like fibril formation of human lysozyme.,Goda S, Takano K, Yamagata Y, Maki S, Namba K, Yutani K J Biochem. 2002 Oct;132(4):655-61. PMID:12359083[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, Totty N, Nguyen O, Blake CC, Terry CJ, et al.. Human lysozyme gene mutations cause hereditary systemic amyloidosis. Nature. 1993 Apr 8;362(6420):553-7. PMID:8464497 doi:http://dx.doi.org/10.1038/362553a0
- ↑ Goda S, Takano K, Yamagata Y, Maki S, Namba K, Yutani K. Elongation in a beta-structure promotes amyloid-like fibril formation of human lysozyme. J Biochem. 2002 Oct;132(4):655-61. PMID:12359083
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