The Infona portal uses cookies, i.e. strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser.
The Notch ankyrin repeat domain contains seven ankyrin sequence repeats, six of which adopt very similar structures. To determine if folding proceeds along parallel pathways and the order in which repeats become structured during folding, we examined the effect of analogous destabilizing Ala→Gly substitutions in each repeat on folding kinetics. We find that folding proceeds to an on-pathway kinetic...
The accurate and effective interpretation of low-resolution data in X-ray crystallography is becoming increasingly important as structural initiatives turn toward large multiprotein complexes. Substantial challenges remain due to the poor information content and ambiguity in the interpretation of electron density maps at low resolution. Here, we describe a semiautomated procedure that employs a restraint-based...
ERp57, in complex with the lectins calreticulin and calnexin, catalyzes disulphide bond formation in N-glycosylated proteins. In this issue of Structure, Kozlov et al. (2006) report the structure of the noncatalytic domains of ERp57 and characterize the calnexin interaction site.
The Escherichia coli Ppx protein is an exopolyphosphatase that degrades long-chain polyphosphates in a highly processive reaction. It also hydrolyzes the terminal 5′ phosphate of the modified nucleotide guanosine 5′ triphosphate 3′ diphosphate (pppGpp). The structure of Ppx has been determined to 1.9 Å resolution by X-ray crystallography. The exopolyphosphatase is an ASKHA (acetate and sugar kinases,...
Deubiquitinating proteases reverse protein ubiquitination and rescue their target proteins from destruction by the proteasome. USP2, a cysteine protease and a member of the ubiquitin specific protease family, is overexpressed in prostate cancer and stabilizes fatty acid synthase, which has been associated with the malignancy of some aggressive prostate cancers. Here, we report the structure of the...
Suppressor of cytokine signaling (SOCS) proteins are indispensable negative regulators of cytokine-stimulated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways. SOCS proteins (SOCS1–7 and CIS) consist of a variable N-terminal region, a central Src homology-2 (SH2) domain, and a C-terminal SOCS box. The N-terminal region in SOCS1 and SOCS3 includes the so-called...
Sirtuin proteins comprise a unique class of NAD + -dependent protein deacetylases. Although several structures of sirtuins have been determined, the mechanism by which NAD + cleavage occurs has remained unclear. We report the structures of ternary complexes containing NAD + and acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm H116Y...
The small GTPase Rab11 regulates the recycling of endosomes to the plasma membrane via interactions with the Rab11 family of interacting proteins (FIPs). FIPs contain a highly conserved Rab binding domain (RBD) at their C termini whose structure is unknown. Here, we have determined the crystal structure of the RBD of FIP2 in complex with Rab11(GTP) by single wavelength anomalous diffraction methods...
Sirtuins catalyze the NAD + -dependent protein deacetylation of lysine residues. In this issue of Structure, Hoff et al. (2006) report the structure of a sirtuin homolog with both substrates bound, providing new insight into the catalytic mechanism.
Three distinct isoforms of pantothenate kinase (CoaA) in bacteria catalyze the first step in coenzyme A biosynthesis. The structures of the type II (Staphylococcus aureus, SaCoaA) and type III (Pseudomonas aeruginosa, PaCoaA) enzymes reveal that they assemble nearly identical subunits with actin-like folds into dimers that exhibit distinct biochemical properties. PaCoaA has a fully enclosed pantothenate...
This paper describes the outcome of a “Workshop on Biological Macromolecular Structure Models” held in November 2005 in which experimentalists and modelers discussed the best way to archive models of biological macromolecules.
The gating mechanism of the open state of the gramicidin A (gA) channel is studied by using a new Monte Carlo Normal Mode Following (MC-NMF) technique, one applicable even without a target structure. The results demonstrate that the lowest-frequency normal mode (NM) at ∼6.5 cm −1 is the crucial mode that initiates dissociation. Perturbing the gA dimer in either direction along this NM leads...
The synthesis of proteins in the endoplasmic reticulum (ER) is limited by the rate of correct disulfide bond formation. This process is carried out by protein disulfide isomerases, a family of ER proteins which includes general enzymes such as PDI that recognize unfolded proteins and others that are selective for specific proteins or classes. Using small-angle X-ray scattering and X-ray crystallography,...
While substrate permeation through monomeric pores of aquaporins is well characterized, little is known about the possible tetrameric pore. AQP1 has been suggested to function as an ion channel upon cGMP activation, although this idea has been controversial. Taking a theoretical and experimental approach, we demonstrate that the current might arise through the tetrameric pore and propose a plausible...
Acyl-amino acids were discovered in the search for novel therapeutic agents produced by uncultured microorganisms. In this issue of Structure, Van Wagoner and Clardy (2006) find that the N-acyl-amino acid synthase FeeM bound to acyl-tyrosine is the latest member of the GCN5-related N-acyltransferase superfamily.
We attempt to classify protein-DNA complexes by using a set of 11 descriptors, mainly characterizing protein-DNA interactions, including the number of atomic contacts at major and minor grooves, conformational deviations from standard B- and A-DNA forms, widths of DNA grooves, GC content, specificity measures of direct and indirect readouts, and buried surface area at the complex interface. The cluster...
To investigate the stability of the open nuclear state of the exportin Cse1p and its closing mechanism at the atomic level, we have performed multiple molecular dynamics simulations. The simulations revealed a strikingly fast transition of Cse1p from the open conformation to the closed cytoplasmic form, consistent with the proposal that Cse1p represents a “spring-loaded molecule.” The structure of...
Riboswitches are noncoding mRNA elements that bind small-molecule metabolites with high affinity and specificity, and they regulate the expression of associated genes. The thi-box riboswitch can exhibit a 1000-fold higher affinity for thiamine pyrophosphate over closely related noncognate compounds such as thiamine monophosphate. To understand the chemical basis of thi-box pyrophosphate specificity,...
Attempts to access antibiotics by capturing biosynthetic genes and pathways directly from environmental DNA, which is overwhelmingly derived from uncultured bacteria, have revealed a large and previously unknown family of N-acyl amino acid synthases (NASs). The structure of the NAS FeeM reveals structural similarity to the GCN5-related N-acyl transferases and acylhomoserine lactone synthases. The...
This paper reports a combined computational and experimental study of the correlation between protein stability cores and folding kinetics. An empirical potential function was developed, and it was used for analyzing interaction energies among secondary structure elements. Studies on a β sandwich protein, Pseudomonas aeruginosa azurin, showed that the computationally identified substructure with the...
Set the date range to filter the displayed results. You can set a starting date, ending date or both. You can enter the dates manually or choose them from the calendar.