Structure
Background: Structural studies of protein-DNA complexes have tended to give the impression that DNA recognition requires a unique molecular interface. However, many proteins recognize DNA targets that differ from what is thought to be their ideal target sequence. The steroid hormone receptors illustrate this problem in recognition rather well, since consensus DNA targets are rare.Results Here we describe...
Background: Lysyl-tRNA synthetase catalyzes the attachment of the amino acid lysine to the cognate tRNA. The enzyme is a member of the class II aminoacyl-tRNA synthetases; the crystal structures of the seryl- and aspartyl-tRNA synthetases from this class are already known. Lysyl-tRNA synthetase shows extensive sequence homology with aspartyl-tRNA synthetase. In Escherichia coli there are two isoforms...
The recently reported crystal structures of two recombination enzymes, the catalytic domain of HIV integrase and Escherichia coli RuvC, an endonuclease, are surprisingly similar to that of ribonuclease H suggesting the possibility that they have a common enzymatic mechanism.
Background: Under moderate pressure, xenon can bind to proteins and form weak but specific interactions. Such protein-xenon complexes can be used as isomorphous derivatives for phase determination in X-ray crystallography.Results Investigation of the serine proteinase class of enzymes shows that the catalytic triad, the common hydrolytic motif of these enzymes, is a specific binding site for one xenon...
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: Human thioredoxin is a 12 kDa cellular redox protein that plays a key role in maintaining the redox environment of the cell. It has recently been shown to be responsible for activating the DNA-binding properties of the cellular transcription factor, NFκB, by reducing a disulfide bond involving Cys62 of the p50 subunit. Using multidimensional heteronuclear-edited and heteronuclear-filtered...
Although the annexins have been extensively studied and much detailed structural information is available, their in vivo function has yet to be established.
The recent high-resolution solution structures of human and Escherichia coli thioredoxin in their oxidized and reduced states support a catalytic model of protein disulfide reduction involving binding of a target protein and nucleophilic attack by the active-site Cys32 thiolate to form a transition state mixed disulfide.
The thioredoxin fold is a characteristic protein structural motif that has been found in five distinct classes of proteins that have the common property of interacting with cysteine-containing substrates.
Background: The mitogen-activated protein (MAP) kinase, ERK2, is a tightly regulated enzyme in the ubiquitous Ras-activated protein kinase cascade. ERK2 is activated by phosphorylation at two sites, Y185 and T183, that lie in the phosphorylation lip at the mouth of the catalytic site. To ascertain the role of these two residues in securing the low-activity conformation of the enzymes we have carried...
Background: The coat protein in RNA bacteriophages binds and encapsidates viral RNA, and also acts as translational repressor of viral replicase by binding to an RNA hairpin in the RNA genome. Because of its dual function, the MS2 coat protein is an interesting candidate for structural studies of protein-RNA interactions and protein-protein interactions. In this study, unassembled MS2 coat protein...
Background: Streptococcal protein G comprises two or three domains that bind to the constant Fc region of most mammalian immunoglobulin Gs (IgGs). Protein G is functionally related to staphylococcal protein A, with which it shares neither sequence nor structural homology.Results To understand the competitive binding of these two proteins to the Fc region, the crystal structure of a single Ig-binding...
Insufficient sampling of conformational sub-states by current molecular dynamics simulations accounts for deficiencies in representations of the fluctuating interatomic separations in macromolecules.
J Ding,
K Das,
C Tantillo,
W Zhang,
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Background: HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that copies the RNA genome of HIV-1 into DNA. It is a heterodimer composed of a 66 kDa (p66) and a 51 kDa (p51) subunit. HIV-1 RT is a crucial target for structure-based drug design, and potent inhibitors have been identified, whose efficacy, however, is limited by drug resistance.Results The crystal structure of HIV-1 RT in...
Background: Little is known of the intermolecular organization of crystallins in the protein-packed eye lens. The tetrameric structure of the 200 000 Da avian δ-crystallin, which is closely related to the enzyme argininosuccinate lyase and is characteristic of the accommodating, soft lens of birds, has recently been solved at atomic resolution at acidic pH. To help understand how δ-crystallin remains...
Background: Seryl-tRNA synthetase is a homodimeric class II aminoacyl-tRNA synthetase that specifically charges cognate tRNAs with serine. In the first step of this two-step reaction, Mg.ATP and serine react to form the activated intermediate, seryl-adenylate. The serine is subsequently transferred to the 3'-end of the tRNA. In common with most other aminoacyl-tRNA synthetases, seryl-tRNA synthetase...
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: Like many viruses, bacteriophage φX174 packages its DNA genome into a procapsid that is assembled from structural intermediates and scaffolding proteins. The procapsid contains the structural proteins F, G and H, as well as the scaffolding proteins B and D. Provirions are formed by packaging of DNA together with the small internal J proteins, while losing at least some of the B scaffolding...
Structures have recently been determined for the yeast Schizosaccharomyces pombe cell cycle regulatory protein, CKS/suc1, and its human equivalent. The structures provide some long-awaited clues about the role of CKS/suc1 in cell cycle control.