Current Medicinal Chemistry - Volume 11, Issue 5, 2004

We live in times of overwhelmingly fast development of new genomics and proteomics methods bringing primary structures of a number of genomes.More than 20,000 protein structures are stored in the protein data bank (PDB),but it is less than one tenth of a number of already defined primary structures of proteins.Even using fastest throughput crystallization and X-ray crystallography methods scientists would not be a Read More

The P450 family of proteins has more than 1000 representatives,which despite sometimes relatively low sequence identity have a surprisingly high level of structural similarity.This fact makes this family of proteins ideal candidate for various types of modeling based on protein structure prediction.A number of P450 proteins,including CYPs 1A1,1A2,1B1,3A4,11B2,17,and 19,play a role in the metabolism of estrogen.Inhibit Read More

Over 1,500 human disease genes have been identified,of which only a small fraction have experimental structural information on the protein products.To better understand the mechanisms of these hereditary diseases,we undertook a systematic study to predict the structures of disease proteins and characterize their interactions with other proteins.This study was facilitated by two tools developed previously:(1) COBLATH Read More

The human genome and other genome sequencing projects have generated huge amounts of protein sequence information.Recently,a structural genomics project that aims to determine at least one representative three-dimensional structure from every protein family experimentally has been started.Homology modeling will play an essential role in structure based drug design such as in silico screening;because based on t Read More

The nicotinic receptor at the motor endplate has served as a prototype for understanding structure,function and ligand recognition in the superfamily of pentameric ligand-gated ion channels.Yet despite this advanced state of knowledge, atomic-scale understanding of such elementary processes as ligand recognition has remained elusive owing to the lack of a high-resolution x-ray structure.However,the field has recentl Read More

We have studied the structure and function of Human Misshapen / NIK-related kinase (MINK-1)through a combination of computational methods and experimental approaches,including (1)fold recognition and sequence-structure alignment for each structural domain using the threading program PROSPECT,(2)gene expression and protein-protein interaction analysis of yeast homologs of human MINK-1 domains,and (3)ye Read More

Homology modeling has become an essential tool for studying proteins that are targets for medical drug design.This paper describes the approach we developed that combines sequence decomposition techniques with distance geometry algorithms for homology modeling to determine functionally important regions of proteins.We show here the application of these techniques to targets of medical interest chosen from t Read More

Rational design in protein engineering leads to significant progresses in medicinal chemistry research.It alleviates the difficulty of exploring unreasonable biological functions.Combining with analysis of biophysical-chemical properties,a three-dimensional (3D)structure provides fruitful information for rational design by revealing functionally important residues.Comparative (homology)modeling,one of the 3D structural p Read More

The Catharanthus (or Vinca )alkaloids comprise a group of about 130 terpenoid indole alkaloids. Vinblastine is now marketed for more than 40 years as an anticancer drug and became a true lead compound for drug development.Due to the pharmaceutical importance and the low content in the plant of vinblastine and the related alkaloid vincristine,Catharanthus roseus became one of the best-studied medicinal plants. Con Read More

Serotonin (5-HT)is involved in various physiological and pathological processes by interaction with 14 distinct receptor subtypes,grouped in seven classes of receptors (5-HT 1-7 )on the basis of amino acid sequence,pharmacology,and signal transduction pathways.The 5-HT 7 R is a G-protein coupled receptor with seven transmembrane domains.It was found by the application of molecular cloning and has been identified in rat Read More