Protein Functional Relationships Research Articles

Conventional teaching remains effective in teaching medical biochemistry in BPKIHS, Nepal, although students enjoy supplementary computer teaching

A computer program down loaded from the Internet was used as a tutorial to teach the structure–function relationship of MHC molecule to MBBS students of BPKIHS, a medical college in Nepal. The computer-aided teaching session, with a facilitator from the biochemistry faculty, was found to be more interesting to the students although learning outcomes were not enhanced by comparison to sessions using only conventional tools. A non-subject expert presenting the computer tutorial failed to generate interest in the topic, and the achievement of learning objectives by the students was inferior. We conclude that the interaction with a biochemistry subject expert was crucial for success in our use of computer-aided teaching sessions on the structure–function relationship of proteins. The results are discussed with attention to the role of computer-aided instruction in medical colleges in a developing country (Nepal).

Protein oxidation and turnover.

All biomacromolecules are faced with oxidative stress. Oxidation of a protein molecule always induces inactivation of the molecule and introduces a tag to that molecule. These modified protein molecules are prone to degradation in vivo by the proteasome system. Coupling of protein modification and degradation of chemically modified proteins is one of the normal protein turnover pathways in vivo. We call this a 'chemical apoptosis' process, which is one of the early manifestations of programmed cell death. Impairment of the proteasome system leads to accumulation of modified nonfunctional proteins or 'aged proteins' that might cause various clinical syndromes including cataractogenesis, premature aging, neurological degeneration and rheumatoid disease. The metal-catalyzed oxidation of biomacromolecules provides an excellent artificial aging system in vitro. The system is very useful in the characterization of structure and function relationships of proteins (enzymes), especially in those containing metal binding domain(s), because the oxidation is always followed by an affinity cleavage at the metal binding site(s) that allows easy identification and further characterization.

Grafting of Protein-Protein Interaction Epitope

Transferring the biological function of one protein to another is a key issue in understanding the structure and function relationship of proteins. We have developed a strategy for grafting protein-protein interaction epitopes. As a first step, residues at the interface of the ligand protein which strongly interact with the receptor protein were identified. Then protein scaffolds were docked onto receptor protein based on geometric complementarity. Only high docking score matches were saved. For each saved match, the scaffold protein was accepted if it had suitable positions for grafting key interaction residues of the ligand protein. These candidate residues were mutated to corresponding residues in the ligand protein at each relevant position and the mutated scaffold protein was co-minimized with receptor protein. Finally, the minimized complexes were evaluated by a scoring function deduced from statistical analysis of rigid binding data sets. As a test case, the binding epitope of barstar, the inhibitor of barnase, was grafted onto smaller proteins. Pheromone Er-1(PDB entry 1erc) has been found to be a good scaffold. The calculated binding free energy for mutated Pheromone Er-1 is equivalent to that of barstar.

Remote contributions to subunit interactions: lessons from adult and fetal hemoglobins

For many years, hemoglobin (Hb) has been a model protein for studies of factors that affect the conformational states of proteins1. Natural Hb variants and recombinant Hbs that possess single amino acid residue substitutions have provided important information on the contributions of specific sites to interactions at the interface between the dimer pairs involved in the allosteric transition as the Hb tetramer moves between its oxy and deoxy conformations2. The recent unexpected finding3 that the interactions between these dimer pairs are much stronger in fetal Hb [HbF; (αγ)2] than in adult Hb [HbA; (αβ)2; see Fig. 1) has opened new avenues for exploration of sequence– function relationships in proteins.

Generation of Multiple Site-Specific Mutations in a Single Polymerase Chain Reaction Product

Site-directed mutagenesis has been very valuable in studying the structure–function relationship of proteins (1). PCR-mediated mutagenesis has been the method of choice in recent years to change the desired amino acid from one to another. Several procedures have been described to achieve the desired mutation using PCR technology (2–13). Although in most of the cases the desired change is only with respect to one amino acid, sometimes one needs to generate several changes in the amino acid sequence to understand the biological function of a given protein. Such a necessity is apparent when one is dealing with a zinc finger class of proteins wherein multiple residues of cysteine and histidine are involved in the coordination of zinc. We have been working over the past several years on the structure–function relationship of a spermatidal specific protein TP2 which appears transiently during mammalian spermiogenesis.

The important contribution of high precision mass spectrometric methods in the study of the structure-function relationship of proteins and enzymes.

The important contribution of high precision mass spectrometric methods in the study of the structure-function relationship of proteins and enzymes.

Protein Misassembly IN VITRO

This chapter provides an overview of the results and concepts that have been put forward in the field of in nitro misassembly (coagulation, aggregation). Considering the posttranslational fate of a protein molecule, polypeptide chains that fail to reach the native state are commonly discarded by appropriate cellular mechanisms, either protein turnover or deposition as aggregates. Over the past 30 years, protein chemists have not shown great interest in these side reactions. They merely tried to avoid them because what fully absorbed their curiosity was the structure function relationship of proteins, and function was exactly what aggregates or precipitates were lacking. Lately, the focus has changed for a number of reasons. This chapter summarizes experimental approaches to a deeper understanding of the physicochemical basis of protein misfolding in vitro and with the solution of the protein folding problem still ahead, one may easily predict that another generation of biochemists will be engaged in trying to find the solution to the misfolding problem, with its physical, cell biological, and medical implications.

New Tools for Probing Protein Structure

A computer–generated representation of the cro represser dimer (shown in orange and white) binding to operator DNA (X–ray coordinates were provided by Brian Matthews, University of Oregon). Understanding the structure–function relationships of proteins is the major challenge of protein biochemistry. Analytic techniques like mass spectrometry, nuclear magnetic resonance, and X–ray crystallography are currently being modified to extend their usefulness in determining protein structure.

The chloroplast thylakoid membrane: Biogenesis, organization of pigments, protein-function relationships and degradation during senescence — a review

Chloroplasten enthalten charakteristische Membranstrukturen, die als Thylakoidmembranen bezeichnet werden, die im Energiestoffwechsel der grunen Pflanzen die Funktion der Energieabsorber fur das Sonnenlicht erfullen und gleichzeitig die absorbierte S rahlungsenergie in fur biochemische Reaktionen verwertbare Energie- und Reduktionsaquivalente umwandeln.