Structure
Background: Foot-and-mouth disease viruses (FMDVs) are members of the picornavirus family and cause an economically important disease of cloven-hoofed animals. To understand the structural basis of antigenic variation in FMDV, we have determined the structures of two viruses closely related to strain O 1 BFS whose structure is known. Results The two new structures are, like O 1 BFS,...
The crystal structure of a bacterial light-harvesting membrane protein complex shows a simple modular design and explains how solar energy is collected and passed on to the reaction centre.
Background: Interleukin (IL)-10 is a cytokine that inhibits production of other regulatory factors, including interferon γ (IFNγ) and IL-2. A dimer of IL-10 is present in solution and is presumed to participate in receptor binding, but the nature of the dimer has not been previously reported. An atomic model is necessary to interpret biological activity of IL-10 and to design mutants with agonistic...
Two recent crystal structures of the tetrameric pterin-4α-carbinolamine dehydratase (PCD)/dimerization cofactor of HNF-1 (DCoH) protein provide fresh insights into how this multifunctional enzyme/transcriptional coactivator works.
Background: The collagenases are members of the family of zinc-dependent enzymes known as the matrix metalloproteinases (MMPs). They are the only proteinases that specifically cleave the collagen triple helix, and are important in a large number of physiological and pathological processes. Structures are known for the N-terminal ‘catalytic’ domain of collagenases MMP-1 and MMP-8 and of stromelysin...
Background: Escherichia coli TEM1 is a penicillinase and belongs to class A β-lactamases. Its naturally occurring mutants are responsible for bacterial resistance to β-lactamin-based antibiotics. X-ray structure determinations show that all class A β-lactamases are similar, but, despite the numerous kinetic investigations, the reaction mechanism of these enzymes is still debated. We address the questions...
The three-dimensional structure of the complex between Rap and the 'Ras-binding domain' of Raf could be the prototype for a G protein-effector interaction.
Background: Wild-type triosephosphate isomerase (TIM) is a very stable dimeric enzyme. This dimer can be converted into a stable monomeric protein (monoTIM) by replacing the 15-residue interface loop (loop-3) by a shorter, 8-residue, loop. The crystal structure of monoTIM shows that two active-site loops (loop-1 and loop-4), which are at the dimer interface in wild-type TIM, have acquired rather different...
Background: Cytochrome c is an integral part of the mitochondrial respiratory chain. It is confined to the intermembrane space of mitochondria, and has the function of transferring electrons between its redox partners. Solution studies of cytochrome c indicate that the conformation of the molecule is sensitive to the ionic strength of the medium.Results The crystal structures of cytochromes c from...
Analysis of tick-borne encephalitis virus E protein reveals considerable structural diversity in the glycoproteins that clothe enveloped viruses and hints at the conformational gyrations in this molecule that lead to viral fusion.
The recently published solution structure of the DNA-binding domain of hSRY in complex with a DNA octamer offers insight into the sex reversal effects of mutations in hSRY and the interaction of all HMG boxes with DNA.
High-sensitivity microcalorimetry is beginning to make an impact on the determination of thermodynamic parameters associated with protein-DNA interactions and the understanding of the relationship of these data to structural details of complex formation.
Background: Glutamate, phenylalanine and leucine dehydrogenases catalyze the NAD(P) + -linked oxidative deamination of L-amino acids to the corresponding 2-oxoacids, and sequence homology between these enzymes clearly indicates the existence of an enzyme superfamily related by divergent evolution. We have undertaken structural studies on a number of members of this family in order to investigate...
Background: Pyruvate kinase (PK) plays a major role in the regulation of glycolysis. Its catalytic activity is controlled by the substrate phosphoenolpyruvate and by one or more allosteric effectors. The crystal structures of the non-allosteric PKs from cat and rabbit muscle are known. We have determined the three-dimensional structure of the allosteric type I PK from Escherichia coli, in order to...
Background: Glutathione transferases (GSTs) constitute a family of isoenzymes that catalyze the conjugation of the tripeptide glutathione with a wide variety of hydrophobic compounds bearing an electrophilic functional group. Recently, a number of X-ray structures have been reported which have defined both the glutathione- and the substrate-binding sites in these enzymes. The structure of the glutathione-free...
Background: Group B coxsackieviruses (CVBs) are etiologic agents of a number of human diseases that range in severity from asymptomatic to lethal infections. They are small, single-stranded RNA icosahedral viruses that belong to the enterovirus genus of the picornavirus family. Structural studies were initiated in light of the information available on the cellular receptors for this virus and to assist...
Background: Urokinase-type plasminogen activator (u-PA) promotes fibrinolysis by catalyzing the conversion of plasminogen to the active protease plasmin via the cleavage of a peptide bond. When localized to the external cell surface it contributes to tissue remodelling and cellular migration; inhibition of its activity impedes the spread of cancer. u-PA has three domains: an N-terminal receptor-binding...
Two crystal structures of the hammerhead ribozyme provide the first atomic-resolution views of an RNA active site, and suggest that the catalytic center may reside in a U-turn motif which was first seen in tRNA P h e .