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==ROLE OF PROLINE RESIDUES IN HUMAN LYSOZYME STABILITY: A SCANNING CALORIMETRIC STUDY COMBINED WITH X-RAY STRUCTURE ANALYSIS OF PROLINE MUTANTS== | |||
<StructureSection load='1lhh' size='340' side='right'caption='[[1lhh]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1lhh]] 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=1LHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LHH FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</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=1lhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lhh OCA], [https://pdbe.org/1lhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lhh RCSB], [https://www.ebi.ac.uk/pdbsum/1lhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lhh ProSAT]</span></td></tr> | ||
</table> | |||
== 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/lh/1lhh_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=1lhh ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
It has been shown that protein stability can be modulated from site-directed mutations that affect the entropy of protein unfolding [Matthews, B. W., Nicholson, H., & Becktel, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 6663-6667]. However, the effect of a specific amino acid replacement on stability highly depends on the location of the mutation site and its environment in the protein structure [Yutani, K., Hayashi, S., Sugisaki, Y., & Ogasahara, K. (1991) Proteins Struct., Funct., Genet. 9, 90-98). To clarify the role of specific proline residues in the thermostability of human lysozyme (h-lysozyme), a series of proline mutants were investigated by means of scanning calorimetry and high-resolution X-ray crystallography. The thermodynamic properties of the mutant and wild-type h-lysozymes are compared and discussed on the basis of their three-dimensional structure. h-Lysozyme contains two proline residues at positions 71 and 103. The Pro71----Gly substitution was found to destabilize h-lysozyme by decreasing the entropic contribution of unfolding by about 2 kcal/mol at 68.8 degrees C. This is consistent with the theoretical expectations for such a substitution. However, the same substitution at position 103 (Pro103----Gly) does not affect h-lysozyme stability, and the thermodynamic properties of the P71G/P103G and P71G mutants are essentially the same. Pro71 which is conserved among lysozymes from other species, appears to be important for stability, whereas Pro103, which is not conserved, does not. These differences are explained in terms of residue accessibility to the solvent and crystallographic B-factor, which reflects the amino acid mobility.(ABSTRACT TRUNCATED AT 250 WORDS) | It has been shown that protein stability can be modulated from site-directed mutations that affect the entropy of protein unfolding [Matthews, B. W., Nicholson, H., & Becktel, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 6663-6667]. However, the effect of a specific amino acid replacement on stability highly depends on the location of the mutation site and its environment in the protein structure [Yutani, K., Hayashi, S., Sugisaki, Y., & Ogasahara, K. (1991) Proteins Struct., Funct., Genet. 9, 90-98). To clarify the role of specific proline residues in the thermostability of human lysozyme (h-lysozyme), a series of proline mutants were investigated by means of scanning calorimetry and high-resolution X-ray crystallography. The thermodynamic properties of the mutant and wild-type h-lysozymes are compared and discussed on the basis of their three-dimensional structure. h-Lysozyme contains two proline residues at positions 71 and 103. The Pro71----Gly substitution was found to destabilize h-lysozyme by decreasing the entropic contribution of unfolding by about 2 kcal/mol at 68.8 degrees C. This is consistent with the theoretical expectations for such a substitution. However, the same substitution at position 103 (Pro103----Gly) does not affect h-lysozyme stability, and the thermodynamic properties of the P71G/P103G and P71G mutants are essentially the same. Pro71 which is conserved among lysozymes from other species, appears to be important for stability, whereas Pro103, which is not conserved, does not. These differences are explained in terms of residue accessibility to the solvent and crystallographic B-factor, which reflects the amino acid mobility.(ABSTRACT TRUNCATED AT 250 WORDS) | ||
Role of proline residues in human lysozyme stability: a scanning calorimetric study combined with X-ray structure analysis of proline mutants.,Herning T, Yutani K, Inaka K, Kuroki R, Matsushima M, Kikuchi M Biochemistry. 1992 Aug 11;31(31):7077-85. PMID:1643041<ref>PMID:1643041</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1lhh" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Lysozyme 3D structures|Lysozyme 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Herning T]] | |||
[[Category: Herning | [[Category: Inaka K]] | ||
[[Category: Inaka | [[Category: Kikuchi M]] | ||
[[Category: Kikuchi | [[Category: Kuroki R]] | ||
[[Category: Kuroki | [[Category: Matsushima M]] | ||
[[Category: Matsushima | [[Category: Yutani K]] | ||
[[Category: Yutani | |||