BACKGROUNDAlthough biomedical ontologies have standardized the representation of gene products across species and databases, a method for determining the functional similarities of gene products has not yet been developed.

METHODSWe proposed a new semantic similarity measure based on Gene Ontology that considers the semantic influences from all of the ancestor terms in a graph. Our measure was compared with Resnik's measure in two applications, which were based on the association of the measure used with the gene co-expression and the protein-protein interactions.

RESULTSThe results showed a considerable association between the semantic similarity and the expression correlation and between the semantic similarity and the protein-protein interactions, and our measure performed the best overall.

CONCLUSIONThese results revealed the potential value of our newly proposed semantic similarity measure in studying the functional relevance of gene products.

Membrane Proteins/metabolism* ; Protein Binding

'Divide and conquer' has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions 'extensions'. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Using bioinformatics, we find that many PDZ domains have potential extensions and we developed an openly-accessible website to display our results ( http://bcz102.ust.hk/pdzex/ ). We propose, using well-studied PDZ domains as illustrative examples, that the roles of PDZ extensions can be classified into at least four categories: 1) protein dynamics-based modulation of target binding affinity, 2) provision of binding sites for macro-molecular assembly, 3) structural integration of multi-domain modules, and 4) expansion of the target ligand-binding pocket. Our review highlights the potential structural and functional importance of domain extensions, highlighting the significance of looking beyond the canonical boundaries of protein domains in general.
Animals ; Binding Sites ; Humans ; Ligands ; PDZ Domains ; Protein Binding ; Protein Multimerization ; Proteins ; chemistry

Neurodegenerative diseases are a group of chronic progressive neuronal damage disorders. The cause is unclear, most of them share a same pathological hallmark with misfold proteins accumulating in neurons. Carboxyl-terminus of Hsc70 interacting protein (CHIP) is a dual functional molecule, which has a N terminal tetratrico peptide repeat (TPR) domain that interacts with Hsc/Hsp70 complex and Hsp90 enabling CHIP to modulate the aberrant protein folding; and a C terminal U-box ubiquitin ligase domain that binds to the 26S subunit of the proteasome involved in protein degradation via ubiqutin-proteasome system. CHIP protein mediates interactions between the chaperone system and the ubiquitin-proteasome system, and plays an important role in maintaining the protein homeostasis in cells. This article reviews the molecular characteristics and physiological functions of CHIP, and its role in cellular metabolism and discusses the relationship between CHIP dysfunction and neurodegenerative diseases.
Animals ; Humans ; Neurodegenerative Diseases ; genetics ; metabolism ; Protein Binding ; Protein Folding ; Proteolysis ; Ubiquitin-Protein Ligases ; genetics ; metabolism

G protein-coupled receptors(GPCRs)represent the largest class of cell surface receptors,mediating wide range of cellular and physiological processes through their transducers,G proteins and the-arrestins participate in almost all pathological processes. Recent technological advances are revolutionizing the utility of cryo-electron microscopy(cryo-EM),leading to a tremendous progress in the structural studies of biological macromolecules and cryo-EM has played a leading role in the structural biology of GPCR signaling complex. New discoveries of high-resolution threedimensional structures of GPCR signaling complexes based on cryo-EM have emerged vigorously,which depict the common structural characteristics of intermolecular interaction between GPCR and G protein complex-the conformational changes of the transmembrane helix 6 of receptors,and also demonstrate the structural basis of G protein subtype selectivity. Single-particle cryo-EM becomes an efficient tool for identifying the molecular mechanism of receptor-ligand interaction,providing important information for understanding GPCR signaling and the structure-based drug design.
Cryoelectron Microscopy ; Protein Binding ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled ; chemistry

Lysozyme (LYSO), as an alkalescent protein micromolecule in living organisms, exhibits important pharmacological actions such as antibiosis, anti-inflammatory, antivirus and enhancing immunity. LYSO can combine with many exogenous and endogenous substances and carry many drugs. This essay summarizes interaction between different kinds of active components of natural medicines and lysozymes, which is significant to comprehensively understand pharmacological mechanism of natural drugs and their transfer and metabolic process in organisms, optimize molecule structures of drugs and increase bioavailability and biological effects of natural drugs.
Humans ; Muramidase ; chemistry ; metabolism ; Pharmaceutical Preparations ; chemistry ; metabolism ; Protein Binding

Animals ; Hepatocytes ; metabolism ; Humans ; Lipoproteins ; metabolism ; Protein Binding ; Proteins ; metabolism

Humans ; Protein Binding ; Receptors, Steroid ; agonists ; antagonists & inhibitors ; metabolism ; physiology

OBJECTIVE: We determined the influence of 3-OMD in the protein binding of levodopa to estimate the effect of 3-OMD on the penetration of levodopa into brain. METHOD: P-glycoprotein in the brain may serve to limit drug penetration into the brain. Because it is not available as an experimental substance, but has similar binding properties with alpha 1 acid glycoprotein(AGP), we used AGP in this study. Additionally, we used blood plasma to see the affinity of plasma binding of levodopa. The final concentration of chemicals used in this study were 125, 250, 500, 1000, 2000, 4000 microgram/l for levodopa and 0, 1250, 5000, 10,000 microgram/l for 3-OMD, 1 mg/l for AGP. The free fraction of levodopa in blood plasma and AGP were separated by ultrafiltration method and determined by beta-counter, respectively. RESULTS: We found that levodopa did not bind with AGP, but only 22-24% from 125 microgram/l to 4000 microgram/l of it bound with blood plasma. The addition of 3-OMD to the blood plasma did not significantly change the binding of levodopa. CONCLUSIONS: We can conclude that 3-OMD does not influence the penetration of levodopa into brain. These small amount of the binding does not expect to influence to other drugs on the binding with plasma.
Brain ; Drug Interactions ; Levodopa* ; P-Glycoprotein ; Plasma* ; Protein Binding ; Ultrafiltration

Monoclonal antibodies have become the main type of antibody drug because of their high specificity and strong affinity to antigen. However, with the intensive study of the natural monoclonal antibody, many defects have faced, such as the limit times of binding to antigen, the unanticipated antibody clearance and antigen accumulation. Therefore, studies are no longer limited to the natural antibody screening, but rather to improve the efficiency of antibody drugs by engineering. In recent years, the bottlenecks in the development of conventional antibody have been solved effectively since the discovery of a novel recycling antibody. Recycling antibody binds to an antigen in plasma and dissociates from the antigen in endosome, thus maximizing the use of antibody and reducing antigen-mediated antibody clearance and antibody-mediated antigen accumulation. In addition, recycling antibodies can enhance the affinity with Fc receptors through further Fc modification. This paper reviews the research progress of circulating antibodies, including its characteristics, transformation methods and prospects.
Antibodies, Monoclonal ; immunology ; Antigens ; Endosomes ; Protein Binding ; Receptors, Fc