Lysozyme Function
Published by Anonymous on 2007/9/29 (5296 reads)
1: Clin Chim Acta. 2005 Jul 24;357(2):168-72.
Lysozyme: a paradigmatic molecule for the investigation of protein structure, function and misfolding.
Merlini G, Bellotti V.
Biotechnology Research Laboratory, University Hospital IRCCS Policlinico San Matteo, Department of Biochemistry, University of Pavia, P.le Golgi, 2, 27100 Pavia, Italy. gmerlini@unipv.it
BACKGROUND: The term amyloidosis encompasses a wide group of conditions characterised by the tissue deposition of autologous proteins assembled in homogeneous regularly spaced antiparallel beta strands. The mechanism by which the different proteins gain a conformation, allowing monomers to bind to each other to form the regular amyloid fibril, is under intensive investigation. The discovery that human lysozyme, a protein thoroughly structurally and functionally characterised, can form amyloid fibrils has offered unique opportunities to unveil the molecular mechanisms involved in amyloid formation. Four amyloidogenic mutations have been identified and an apparently non-amyloidogenic polymorphism has been recently described. RESULTS AND CONCLUSIONS: Lysozyme is well characterised for structure, function, folding dynamics and metabolism and comparative studies are becoming available that highlight pathogenic differences between the wild-type and the amyloidogenic variants. The chemical structure of lysozyme in natural amyloid fibrils was characterised in high detail in the early cases, but it is still lacking in the cases most recently discovered. Amyloidogenic lysozymes represent a prototypic molecule for new pharmaceutical approaches in which the formation of amyloid fibrils is abrogated through a stabilisation of the precursor.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15913589 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: FASEB J. 1996 Jan;10(1):35-41.
Structural and genetic analysis of the folding and function of T4 lysozyme.
Matthews BW.
Institute of Molecular Biology, Howard Hughes Medical Institute, Eugene, Oregon, USA.
The combination of directed mutagenesis with high-resolution structure analysis has made it possible to systematically address fundamental questions of protein folding and stability. Here we briefly review some recent results in this area based on studies of the lysozyme of bacteriophage T4. Extended segments of the polypeptide chain can be substituted with alanine, suggesting that about 50%, or perhaps less, of the overall amino acid sequence protein is necessary to define the 3-dimensional structure of the protein. It is the internal residues that seem to be most important for folding and stability (although not necessarily for function). Substitutions within the core of the protein of large nonpolar side chains with smaller ones have been used to better understand the nature of hydrophobic stabilization. Mutants that produce the largest cavities within the protein tend to be most destabilizing, allowing the energy cost of cavity formation to be estimated. Small, nonpolar ligands bind within such cavities and restore some stability to the protein. Analogous, nonpolar ligands do not bind, however, providing evidence that water molecules do not bind with high occupancy within nonpolar cavities. In a further series of studies it has been possible to re-engineer the active site region of T4 lysozyme to change the catalytic mechanism of the enzyme.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 8566545 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: J Bacteriol. 1994 Nov;176(22):6783-8.
Genetic analysis of bacteriophage T4 lysozyme structure and function.
Poteete AR, Hardy LW.
Department of Molecular Genetics & Microbiology, University of Massachusetts Medical Center, Worcester.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 7961435 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Protein Eng. 1994 Jun;7(6):735-42.
From genesis to function of proteins: investigation of general principles by engineering human lysozyme.
Kikuchi M, Ikehara M.
Protein Engineering Research Institute, Osaka, Japan.
Publication Types:
Review
PMID: 7937703 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Adv Protein Chem. 1991;41:173-315.
Lysozyme and alpha-lactalbumin: structure, function, and interrelationships.
McKenzie HA, White FH Jr.
Department of Chemistry, University College, University of New South Wales, Australian Defence Force Academy, Canberra, ACT, Australia.
Publication Types:
Review
PMID: 2069076 [PubMed - indexed for MEDLINE]
Lysozyme: a paradigmatic molecule for the investigation of protein structure, function and misfolding.
Merlini G, Bellotti V.
Biotechnology Research Laboratory, University Hospital IRCCS Policlinico San Matteo, Department of Biochemistry, University of Pavia, P.le Golgi, 2, 27100 Pavia, Italy. gmerlini@unipv.it
BACKGROUND: The term amyloidosis encompasses a wide group of conditions characterised by the tissue deposition of autologous proteins assembled in homogeneous regularly spaced antiparallel beta strands. The mechanism by which the different proteins gain a conformation, allowing monomers to bind to each other to form the regular amyloid fibril, is under intensive investigation. The discovery that human lysozyme, a protein thoroughly structurally and functionally characterised, can form amyloid fibrils has offered unique opportunities to unveil the molecular mechanisms involved in amyloid formation. Four amyloidogenic mutations have been identified and an apparently non-amyloidogenic polymorphism has been recently described. RESULTS AND CONCLUSIONS: Lysozyme is well characterised for structure, function, folding dynamics and metabolism and comparative studies are becoming available that highlight pathogenic differences between the wild-type and the amyloidogenic variants. The chemical structure of lysozyme in natural amyloid fibrils was characterised in high detail in the early cases, but it is still lacking in the cases most recently discovered. Amyloidogenic lysozymes represent a prototypic molecule for new pharmaceutical approaches in which the formation of amyloid fibrils is abrogated through a stabilisation of the precursor.
Publication Types:
Research Support, Non-U.S. Gov't
Review
PMID: 15913589 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
2: FASEB J. 1996 Jan;10(1):35-41.
Structural and genetic analysis of the folding and function of T4 lysozyme.
Matthews BW.
Institute of Molecular Biology, Howard Hughes Medical Institute, Eugene, Oregon, USA.
The combination of directed mutagenesis with high-resolution structure analysis has made it possible to systematically address fundamental questions of protein folding and stability. Here we briefly review some recent results in this area based on studies of the lysozyme of bacteriophage T4. Extended segments of the polypeptide chain can be substituted with alanine, suggesting that about 50%, or perhaps less, of the overall amino acid sequence protein is necessary to define the 3-dimensional structure of the protein. It is the internal residues that seem to be most important for folding and stability (although not necessarily for function). Substitutions within the core of the protein of large nonpolar side chains with smaller ones have been used to better understand the nature of hydrophobic stabilization. Mutants that produce the largest cavities within the protein tend to be most destabilizing, allowing the energy cost of cavity formation to be estimated. Small, nonpolar ligands bind within such cavities and restore some stability to the protein. Analogous, nonpolar ligands do not bind, however, providing evidence that water molecules do not bind with high occupancy within nonpolar cavities. In a further series of studies it has been possible to re-engineer the active site region of T4 lysozyme to change the catalytic mechanism of the enzyme.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 8566545 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
3: J Bacteriol. 1994 Nov;176(22):6783-8.
Genetic analysis of bacteriophage T4 lysozyme structure and function.
Poteete AR, Hardy LW.
Department of Molecular Genetics & Microbiology, University of Massachusetts Medical Center, Worcester.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review
PMID: 7961435 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
4: Protein Eng. 1994 Jun;7(6):735-42.
From genesis to function of proteins: investigation of general principles by engineering human lysozyme.
Kikuchi M, Ikehara M.
Protein Engineering Research Institute, Osaka, Japan.
Publication Types:
Review
PMID: 7937703 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------------------------
5: Adv Protein Chem. 1991;41:173-315.
Lysozyme and alpha-lactalbumin: structure, function, and interrelationships.
McKenzie HA, White FH Jr.
Department of Chemistry, University College, University of New South Wales, Australian Defence Force Academy, Canberra, ACT, Australia.
Publication Types:
Review
PMID: 2069076 [PubMed - indexed for MEDLINE]
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