Current Protein and Peptide Science - Volume 9, Issue 4, 2008

Different methods for describing and comparing the structures of the tens of thousands of proteins that have been determined by X-ray crystallography are reviewed. Such comparisons are important for understanding the structures and functions of proteins and facilitating structure prediction, as well as assessing structure prediction methods. We summarize methods in this field emphasizing ways of representing protein structures as one-dimensional geometrical strings. Such strings are based on the shape symbols of clustered regions of φ/Ψ dihedral angle pairs of the polypeptide backbones as described by the Ramachandran plot. These one-dimensional expressions are as compact as secondary structure description but contain more information in loop regions. They can be used for fast searching for similar structures in databases and for comparing similarities between proteins and between the predicted and native structures.

Glutathione Transferases (GSTs) are crucial enzymes in the cell detoxification process catalyzing the nucleophilic attack of glutathione (GSH) on toxic electrophilic substrates and producing a less dangerous compound. GSTs studies are of great importance since they have been implicated in the development of drug resistance in tumoral cells and are related to human diseases such as Parkinson's, Alzheimer's, atherosclerois, liver cirrhosis, aging and cataract formation. In this review we start by providing an evolutionary perspective of the mammalian cytosolic GSTs known to date. Later on we focus on the more abundant classes alpha, mu and pi and their structure, catalysis, metabolic associated functions, drug resistance relation and inhibition methods. Finally, we introduce the recent insights on the GST class zeta from a metabolic perspective.

Green fluorescent protein (GFP) from jellyfish Aequorea victoria is the most extensively studied and widely used in cell biology protein. GFP-like proteins constitute a fast growing family as several naturally occurring GFP-like proteins have been discovered and enhanced mutants of Aequorea GFP have been created. These mutants differ from wild-type GFP by conformational stability, quantum yield, spectroscopic properties (positions of absorption and fluorescence spectra) and by photochemical properties. GFP-like proteins are very diverse, as they can be not only green, but also blue, orange-red, far-red, cyan, and yellow. They also can have dual-color fluorescence (e.g., green and red) or be nonfluorescent. Some of them possess kindling property, some are photoactivatable, and some are photoswitchable. This review is an attempt to characterize the main color groups of GFP-like proteins, describe their structure and mechanisms of chromophore formation, systemize data on their conformational stability and summarize the main trends of their utilization as markers and biosensors in cell and molecular biology.

Pancreatic-type ribonucleases are a family of RNA degrading enzymes that share different degrees of sequence identity but a very similar 3D-structure. The prototype of this family is bovine pancreatic ribonuclease or ribonuclease A. This enzyme has been the object of landmark work on the folding, stability, protein chemistry, catalysis, enzyme-substrate interaction and molecular evolution. In the recent years, the interest in the study of pancreatic-type ribonucleases has increased due to the involvement of some members of this family in special biological functions. In addition, dimeric and also higher oligomeric structures can be attained by the members of this family. The oligomers described structurally to date are mainly formed by 3D-domain swapping, a process which consists of the exchange of identical domains (i.e. identical structural elements, usually the N- and C-termini) between the subunits and is considered to be a mechanism for amyloid-type aggregate formation. This review compares the dimeric and oligomeric structures of different members of the pancreatic-type ribonuclease family which are able to acquire these structures, namely, bovine seminal ribonuclease, ribonuclease A and its human counterpart, human pancreatic ribonuclease. A specific focus is placed on what is known about the structural determinants that lead to the acquisition of a particular oligomeric structure and on the proposed mechanism of 3D-swapping.

Protein-protein interface prediction is a booming field, with a substantial growth in the number of new methods being published the last two years. The increasing number of available three-dimensional structures of protein-protein complexes has enabled large-scale statistical analyses of protein interfaces, considering evolutionary, physicochemical and structural properties. Successful combinations of these properties have led to more accurate interface predictors in recent years. In addition to parametric combination, machine learning algorithms have become popular. In the meantime, assessing the absolute and relative performance of interface predictors remains very difficult: This is due to differences in both the output of the various interface predictors, and in the evaluation criteria used by their respective authors. This review provides an overview of the state of the art in the field, and discusses the performance of existing interface predictors. The focus is mainly on protein-protein interface prediction, although most issues are also valid for other kinds of interface prediction.

Pure organic solvents or mixtures with water are very common environments for studying protein and peptide in solution. These milieu conditions are used either for improving the catalytic performance of enzymes or for studying the effect of solvent on the protein stability and hence gaining insight into the protein folding mechanism. The atomic details of these processes are mainly addressed using computer simulation approaches. In particular, Molecular Dynamics simulation represents the most powerful and versatile tool to investigate the details of solvation processes at atomic level. In the last few years, the number of publications peptide and protein simulations in non-natural environments has proliferated. These studies are providing important contributions to shed light on the nature of non-aqueous solvent effects. In this review, the achievements and the future prospects in this field of computational biochemistry are reviewed by summarizing the most important theoretical results published in the last 10 years.