Structure
Background: The flexibility of DNA enables it to adopt three interconvertible types of duplex termed the A-, B- and Z-forms. It can also produce hairpin loops, triplex structures and guanine-rich quadruplex structures. Conformational flexibility assists in the tight packaging of DNA, for example in chromosomes. This is important given the large quantity of genetic information that must be packaged...
Background: Titin is a gigantic protein located in the thick filament of vertebrate muscles. The putative functions of titin range from interactions with myosin and other muscle proteins to a role in muscle recoil. Analysis of its complete sequence has shown that titin is a multi-domain protein containing several copies of modules of 100 amino acids each. These are thought to belong to the fibronectin...
Background: Tetrahydrobiopterin serves as the cofactor for enzymes involved in neurotransmitter biosynthesis and as a regulatory factor in immune cell proliferation and the biosynthesis of melanin. The biosynthetic pathway to tetrahydrobiopterin consists of three steps starting from GTP. The initial reaction is catalyzed by GTP cyclohydrolase I (GTP-CH-I) and involves the chemically complex transformation...
Background: Control of intracellular events by protein phosphorylation is promoted by specific protein kinases. All the known protein kinases possess a common structure that defines a catalytically competent entity termed the ‘kinase catalytic core’. Within this common structural framework each kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by...
The crystal structure of the N-terminal domain of neural cadherin provides the first atomic-level picture of interacting cell-adhesion molecules, and suggests a mechanism for assembly and disassembly of intercellular adhesion zones.
Background: The principal human estrogen, 17β-estradiol, is a potent stimulator of certain endocrine-dependent forms of breast cancer. Because human estrogenic 17β-hydroxysteroid dehydrogenase (type I 17β-HSD) catalyzes the last step in the biosynthesis of 17β-estradiol from the less potent estrogen, estrone, it is an attractive target for the design of inhibitors of estrogen production and tumor...
Background: Insect defensin A is a basic 4 kDa protein secreted by Phormia terranovae larvae in response to bacterial challenges or injuries. Previous biological tests suggest that the bacterial cytoplasmic membrane is the target of defensin A. The structural study of this protein is the first step towards establishing a structure–activity relationship and forms the basis for understanding its antibiotic...
Background: Catalase is a ubiquitous enzyme present in both the prokaryotic and eukaryotic cells of aerobic organisms. It serves, in part, to protect the cell from the toxic effects of small peroxides. Escherichia coli produces two catalases, HPI and HPII, that are quite distinct from other catalases in physical structure and catalytic properties. HPII, studied in this work, is encoded by the katE...
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...
The structure of the proteasome from Thermoplasma acidophilum introduces threonine proteases as a fifth class of proteolytic enzymes, and offers insights into the catalytic activity of this complicated piece of molecular machinery with its 14 active sites.
The phosphotyrosine-binding (PTB) domain, recently identified in a number of proteins, specifically recognizes tyrosine-phosphorylated sequences in other proteins. Although similar in function to the well-studied SH2 domain, the PTB domain appears to be structurally unrelated.
Background: Endo-β-N-acetylglucosaminidase H (Endo H), an endoglycosidase secreted by Streptomyces plicatus, hydrolyzes the glycosidic bond between the core N-acetylglucosamine residues of asparagine-linked high-mannose oligosaccharides. Endo H is a commonly used reagent in glycobiology research, including the characterization of oligosaccharides in glycoproteins. On-going crystallographic studies...
Background: Haemopexin is a serum glycoprotein that binds haem reversibly and delivers it to the liver where it is taken up by receptor-mediated endocytosis. Haemopexin has two homologous domains, each having a characteristic fourfold internal sequence repeat. Haemopexin-type domains are also found in other proteins, including the serum adhesion protein vitronectin and various collagenases, in which...
The structures of the C-terminal domains of rabbit haemopexin and full-length porcine fibroblast collagenase reveal a common β-propeller fold with pseudo-fourfold symmetry. The interactions of these haemopexin-like domains with target proteins and ligands is, however, still a matter of debate.
Background: Lys B28 Pro B29 -human insulin (Humalog TM ), a fully potent insulin analog in which the prolyl, lysyl sequence at the C-terminal end of the B-chain is inverted, exhibits a decreased association of monomers to dimers leading to rapid in vivo absorption. This provides important benefits for the insulin-requiring diabetic. In spite of its monomeric nature, Lys ...
Background: HIV-1 protease (HIV PR), an aspartic protease, cleaves Phe–Pro bonds in the Gag and Gag–Pol viral polyproteins. Substrate-based peptide mimics constitute a major class of inhibitors of HIV PR presently being developed for AIDS treatment. One such compound, KNI-272, which incorporates allophenylnorstatine (Apns)–thioproline (Thp) in place of Phe–Pro, has potent antiviral activity and is...
Background: Because agents which inhibit the receptor binding of cholera toxin constitute possible lead compounds for the structure-based design of anti-cholera drugs, detailed investigation of the toxin's receptor-binding site is of key importance. The substitution Gly→Asp at residue 33 of the cholera toxin B subunit (CTB) has been reported to abolish receptor-binding ability. The substitution Arg35→Asp...