An Italian contribution to structural genomics: Understanding metalloproteins

被引:14
作者
Arnesano, Fabio
Banci, Lucia
Bertini, Ivano
Capozzi, Francesco
Ciofi-Baffoni, Simone
Ciurli, Stefano
Luchinat, Claudio
Mangani, Stefano
Rosato, Antonio
Turano, Paola
Viezzoli, Maria Silvia
机构
[1] Univ Florence, Magnet Resonance Ctr CERM, I-50019 Sesto Fiorentino, Italy
[2] Univ Florence, Dept Chem, I-50019 Sesto Fiorentino, Italy
[3] Univ Bologna, Dept Food Sci, I-47023 Cesena, Italy
[4] Univ Bologna, Dept Agroenvironm Sci & Technol, I-40127 Bologna, Italy
[5] Univ Florence, Dept Agr Biotechnol, I-50144 Florence, Italy
[6] Univ Siena, Dept Chem, I-53100 Siena, Italy
关键词
structural genomics; metalloproteins; protein structure;
D O I
10.1016/j.ccr.2006.01.008
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
In this review, the contribution of the Magnetic Resonance Center of the University of Florence (CERM) to structural genomics is described. This contribution focuses on metalloproteins. Particular emphasis is given to those metalloproteins that belong to the same biochemical pathway, such as the proteins involved in copper trafficking, in metal detoxification, in the assembly of cytochrome c oxidase, and in the assembly of the urease nickel cofactor. Calcium-dependent signalling proteins studied at CERM are also reviewed, for their peculiar conformational features that are at the basis of the signalling process as well as for the importance of the methodological NMR approach based on the substitution of calcium with lanthanide ions. The structural determination in solution of iron-sulfur proteins and cytochromes was pioneered by us in a pre-genomic era and constitutes the methodological basis of the subsequent studies. Our methodological approach is indeed largely based on NMR, even if not exclusively, with important contributions deriving also from X-ray crystallography and X-ray absorption spectroscopy. The use of NMR is particularly useful for the characterization of proteins that occur in vivo as largely of completely unfolded, or that can become unfolded under extreme solution conditions or upon chemical manipulations. Examples in this sense are provided for the different classes of metal binding proteins and in particular for cytochromes and CuZn superoxide dismutase. Within the worldwide frame of structural genomics, we are pursuing also the characterization of known naturally occurring pathogenic mutations. As the three-dimensional structures provided by structural genomics projects constitute a starting database for post-genomic drug design, mention is also made to the perspectives in this field by reviewing our activity. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:1419 / 1450
页数:32
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