Structure
The cyclin-dependent kinases (CDKs) are among the most highly regulated enzymes in the protein-kinase family. The crystal structures of cyclin A and the CDK2-cyclin A complex spectacularly reveal the atomic basis for regulation of these enzymes and provide a template for understanding the function and regulation of other members of the CDK family.
Background: Eukaryotic cell cycle progression is regulated by cyclin dependent protein kinases (CDKs) whose activity is regulated by association with cyclins and by reversible phosphorylation. Cyclins also determine the subcellular location and substrate specificity of CDKs. Cyclins exhibit diverse sequences but all share homology over a region of approximately 100 amino acids, termed the cyclin box...
Background: The human 'protective protein' (HPP) forms a multi-enzyme complex with β-galactosidase and neuraminidase in the lysosomes, protecting these two glycosidases from degradation. In humans, deficiency of HPP leads to the lysosomal storage disease galactosialidosis. Proteolytic cleavage of the precursor form of HPP involves removal of a 2 kDa excision peptide and results in a carboxypeptidase...
The recent determination of the crystal structures of both cyclin A and the cyclin A-CDK2 complex provides new insight into the cyclin-dependent activation of cyclin-dependent protein kinases.
The first three co-crystal structures of homeodomain dimers show that there is more than one way for homeodomains to associate with each other on DNA.
Background: Cytochrome c peroxidase from Pseudomonas aeruginosa (PsCCP) represents a new class of peroxidases which work without the need to create a semi-stable free radical for catalysis. The enzyme is located in the bacterial periplasm where its likely function is to provide protection against toxic peroxides. The soluble 323-residue single polypeptide chain contains two covalent c-type haems with...
Background: Electron transfer between cytochrome f and photosystem I (PSI) can be accomplished by the heme-containing protein cytochrome c 6 or by the copper-containing protein plastocyanin. Higher plants use plastocyanin as the only electron donor to PSI, whereas most green algae and cyanobacteria can use either, with similar kinetics, depending on the copper concentration in the culture...
The first three-dimensional structure of copper amine oxidase demonstrates that one tyrosine residue is converted into 2,4,5-trihydroxyphenylalanine quinone (TPQ). TPQ binds to copper in the inactive form of the enzyme but not in the active form.
Background: The pleckstrin homology (PH) domain, which is approximately 100 amino acids long, has been found in about 70 proteins involved in signal transduction and cytoskeletal function, a frequency comparable to SH2 (src homology 2) and SH3 domains. PH domains have been shown to bind the βγ-subunits of G-proteins and phosphatidylinositol 4,5-bisphosphate (PIP 2 ). It is conceivable that...
Background: The hyperthermophile Pyrococcus furiosus is one of the most thermostable organisms known, with an optimum growth temperature of 100 o C. The proteins from this organism display extreme thermostability. We have undertaken the structure determination of glutamate dehydrogenase from P. furiosus in order to gain further insights into the relationship between molecular structure and...
Background: Sialidases, or neuraminidases, have been implicated in the pathogenesis of many diseases, but are also produced by many non-pathogenic bacteria. Bacterial sialidases are very variable in size, often possessing domains in addition to the catalytic domain. The sialidase from the non-pathogenic soil bacterium Micromonospora viridifaciens is secreted in two forms with molecular weights of...
Background: Copper amine oxidases are a ubiquitous and novel group of quinoenzymes that catalyze the oxidative deamination of primary amines to the corresponding aldehydes, with concomitant reduction of molecular oxygen to hydrogen peroxide. The enzymes are dimers of identical 70-90 kDa subunits, each of which contains a single copper ion and a covalently bound cofactor formed by the post-translational...
Background: Infections caused by Candida albicans, a common fungal pathogen of humans, are increasing in incidence, necessitating development of new therapeutic drugs. Secreted aspartic proteinase (SAP) activity is considered an important virulence factor in these infections and might offer a suitable target for drug design. Amongst the various SAP isozymes, the SAP2 gene product is the major form...
Could the recent elucidation of the structure of the Rap-Raf complex have been the first glimpse of a universal arrangement between GTPase switches and kinase cascades, as a number of recent reports show that Ras is not unique in its ability to start a signalling 'chain reaction'?
Background: Nucleoside diphosphate (NDP) kinases provide precursors for DNA and RNA synthesis. In mammals, these enzymes are also involved in cell regulations. Human NDP kinase B, product of the human nm23-H2 gene, is both an enzyme and a transcription factor. It activates transcription of the c-myc oncogene independently of its catalytic function, by binding to its promoter DNA. How do the two functions...
Background: The Charcot-Leyden crystal (CLC) protein is a major autocrystallizing constituent of human eosinophils and basophils, comprising ~10% of the total cellular protein in these granulocytes. Identification of the distinctive hexagonal bipyramidal crystals of CLC protein in body fluids and secretions has long been considered a hallmark of eosinophil-associated allergic inflammation. Although...
LIM domains are two-zinc-finger structures found in proteins that have diverse functions. They are proposed to be protein dimerization motifs that assemble protein complexes necessary for growth, development and adaptive responses.