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Background: The movement of lipids between membranes is aided by lipid-transfer proteins (LTPs). Some LTPs exhibit broad specificity, transferring many classes of lipids, and are termed non-specific LTPs (ns-LTPs). Despite their apparently similar mode of action, no sequence homology exists between mammalian and plant ns-LTPs and no three-dimensional structure has been reported for any plant ns-LTP...
Background: Candida cylindracea cholesterol esterase (CE) reversibly hydrolyzes cholesteryl linoleate and oleate. CE belongs to the same α/β hydrolase superfamily as triacylglycerol acyl hydrolases and cholinesterases. Other members of the family that have been studied by X-ray crystallography include Torpedo californica acetylcholinesterase, Geotrichum candidum lipase and Candida rugosa lipase. CE...
Background: The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). Two subtypes of the virus, HIV-1 and HIV-2, have been characterized. The protease enzymes from these two subtypes, which are aspartic acid proteases and have been found to be essential for maturation of the infectious particle, share about 50% sequence identity. Differences in substrate...
Background: There are 17 crystal structures of nucleoside monophosphate kinases known. As expected for kinases, they show large conformational changes upon binding of substrates. These are concentrated in two chain segments, or domains, of 30 and 38 residues that are involved in binding of the substrates N 1 TP and N 2 MP (nucleoside tri- and monophosphates with bases N 1 and...
Background: β-glucosidases occur in a variety of organisms and catalyze the hydrolysis of aryl and alkyl-β-D-glucosides as well as glucosides with only a carbohydrate moiety (such as cellobiose). The cyanogenic β-glucosidase from white clover (subsequently referred to as CBG) is responsible for the cleavage of cyanoglucosides. Both CBG and the cyanoglucosides occur within the plant cell wall where...
Background: Cellulases are glycosyl hydrolases — enzymes that hydrolyze glycosidic bonds. They have been widely studied using biochemical and microbiological techniques and have attracted industrial interest because of their potential in biomass conversion and in the paper and textile industries. Glycosyl hydrolases have lately been assigned to specific families on the basis of similarities in their...
Background: The enzyme 6-phospho-β-galactosidase hydrolyzes phospholactose, the product of a phosphoenolpyruvate-dependent phosphotransferase system. It belongs to glycosidase family 1 and no structure has yet been published for a member of this family. Results The crystal structure of 6-phospho-β-galactosidase was determined at 2.3 å resolution by multiple isomorphous replacement, using the wild-type...
Background: Thioredoxins are ubiquitous proteins that serve as reducing agents and general protein disulfide reductases. The structures of thioredoxins from a number of species, including man and Escherichia coli, are known. Cyanobacteria, such as Anabaena, contain two thioredoxins that exhibit very different activities with target enzymes and share little sequence similarity. Thioredoxin-2 (Trx-2)...
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: Type I DNA topoisomerases, divided mechanistically into two subfamilies, are ubiquitous enzymes that participate in replication and transcription. In addition to its role in these fundamental processes, the biological importance of eukaryotic DNA topoisomerase I is underscored by its identification as the target of the antitumor alkaloid camptothecin. An understanding of the mechanism...
Background: Maltoporin (which is encoded by the lamB gene) facilitates the translocation of maltodextrins across the outer membrane of E. coli. In particular, it is indispensable for the transport of long maltooligosaccharides, as these do not pass through non-specific porins. An understanding of this intriguing capability requires elucidation of the structural basis. Results The crystal structures...
Background: Adenylate kinases undergo large conformational changes during their catalytic cycle. Because these changes have been studied by comparison of structures from different species, which share approximately one-third of their residues, only rough descriptions have been possible to date. Results We have solved the structure of unligated adenylate kinase from Escherichia coli at 2.2 å resolution...
Background: Cellulases, which catalyze the hydrolysis of glycosidic bonds in cellulose, can be classified into several different protein families. Endoglucanase CelA is a member of glycosyl hydrolase family 8, a family for which no structural information was previously available.Results The crystal structure of CelA was determined by multiple isomorphous replacement and refined to 1.65 a resolution...
Background: p13 suc1 from fission yeast is a member of the CDC28 kinase specific (CKS) class of cell-cycle control proteins, that includes CKS1 from budding yeast and the human homologues CksHs1 and CksHs2. p13 suc1 participates in the regulation of p34 cdc2 , a cyclin-dependent kinase controlling the G 1 -S and the G ...
Background: The octaheme cytochrome c 3 (M r 26000; cc 3 ) from Desulfovibrio desulfuricans Norway is a dimeric cytochrome made up of two identical subunits, each containing four heme groups. It is involved in the redox transfer chain of sulfate-reducing bacteria, which links the periplasmic oxidation of hydrogen to the cytoplasmic reduction of sulfate. The amino-acid sequence...
Background: Cholera toxin from Vibrio cholerae and the type I heat-labile enterotoxins (LT-Is) from Escherichia coli are oligomeric proteins with AB 5 structures. The type II heat-labile enterotoxins (LT-IIs) from E. coli are structurally similar to, but antigenically distinct from, the type I enterotoxins. The A subunits of type I and type II enterotoxins are homologous and activate adenylate...
Background The steroid hormone 17β-estradiol is important in the genesis and development of human breast cancer. Its intracellular concentration is regulated by 17β-hydroxysteroid dehydrogenase, which catalyzes the reversible reduction of estrone to 17β-estradiol. This enzyme is thus an important target for inhibitor design. The precise localization and orientation of the substrate and cofactor in...
Background Cysteine proteases are involved in a variety of cellular processes including cartilage degradation in arthritis, the progression of Alzheimer's disease and cancer invasion: these enzymes are therefore of immense biological importance. Caricain is the most basic of the cysteine proteases found in the latex of Carica papaya. It is a member of the papain superfamily and is homologous to other...
Background α-Amylases catalyze the hydrolysis of glycosidic linkages in starch and other related polysaccharides. The α-amylase inhibitor (α-AI) from the bean Phaseolus vulgaris belongs to a family of plant defence proteins and is a potent inhibitor of mammalian α-amylases. The structure of pig pancreatic α-amylase (PPA) in complex with both a carbohydrate inhibitor (acarbose) and a proteinaceous...
Background: The differential expression of the ompF and ompC genes is regulated by two proteins that belong to the two component family of signal transduction proteins: the histidine kinase, EnvZ, and the response regulator, OmpR. OmpR belongs to a subfamily of at least 50 response regulators with homologous C-terminal DNA-binding domains of approximately 98 amino acids. Sequence homology with DNA-binding...
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