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.
Mycobacteria have a unique cell wall consisting of mycolic acids, very-long-chain lipids that provide protection and allow the bacteria to persist within human macrophages. Inhibition of cell wall biosynthesis is fatal for the organism and a starting point for the discovery and development of novel antibiotics. We determined the crystal structures of KasA, a key enzyme involved in the biosynthesis...
Besides its function as an essential redox cofactor, nicotinamide adenine dinucleotide (NAD) also serves as a consumable substrate for several reactions with broad impact on many cellular processes. NAD homeostasis appears to be tightly controlled, but the mechanism of its regulation is little understood. Here we demonstrate that a previously predicted bacterial transcriptional regulator, NrtR, represses...
We recently determined the crystal structure of the functional core of human U1 snRNP, consisting of nine proteins and one RNA, based on a 5.5 Å resolution electron density map. At 5–7 Å resolution, α helices and β sheets appear as rods and slabs, respectively, hence it is not possible to determine protein fold de novo. Using inverse beam geometry, accurate anomalous signals were obtained from weakly...
Human DNA polymerase-ι (Polι) incorporates correct nucleotides opposite template purines with a much higher efficiency and fidelity than opposite template pyrimidines. In fact, the fidelity opposite template T is so poor that Polι inserts an incorrect dGTP approximately 10 times better than it inserts the correct dATP. We determine here how a template T/U is accommodated in the Polι active site and...
Mn 2+ -assisted catalysis by B. stearothermophilus TrpRS parallels that in polymerases and reduces specificity in amino acid activation. As predicted by nonequilibrium molecular dynamics simulations, multivariant thermodynamic cycles with [ATP]-dependent Michaelis-Menten kinetics and Mn 2+ for Mg 2+ substitution demonstrate energetic coupling of ATP affinities to the metal;...
The oxygen-dependent hydroxylation of proline residues in the α subunit of hypoxia-inducible transcription factor (HIFα) is central to the hypoxic response in animals. Prolyl hydroxylation of HIFα increases its binding to the von Hippel-Lindau protein (pVHL), so signaling for degradation via the ubiquitin-proteasome system. The HIF prolyl hydroxylases (PHDs, prolyl hydroxylase domain enzymes) are...
DsbD transmembrane protein dispatches electrons to periplasmic Trx/DsbE-like partners via specific interactions with its N-terminal domain, nDsbD. In the present study, PilB N-terminal domain (NterPilB) is shown to efficiently accept electrons coming from nDsbD from Neisseria meningitidis. Using an NMR-driven docking approach, we have modeled the structure of a mixed disulfide complex between NterPilB...
Hydroxylation of two proline residues in hypoxia inducible factor Hif-1α is a key step in the response to hypoxia. Here, Chowdury et al. (2009) elucidate the structural basis of this process by describing a structure for prolyl hydroxylase PHD2 bound to a peptide substrate.
Many neuropeptides and peptide hormones require amidation of their carboxy terminal for full biological activity. The enzyme peptidyl-α-hydroxyglycine α-amidating lyase (PAL; EC 4.3.2.5) catalyzes the second and last step of this reaction, N-dealkylation of the peptidyl-α-hydroxyglycine to generate the α-amidated peptide and glyoxylate. Here we report the X-ray crystal structure of the PAL catalytic...
In a recent issue of Molecular Cell, Das et al. (2009) show that the G2BR domain of gp78, a RING-family E3 ubiquitin ligase, binds the E2 Ube2g2 and induces conformational changes within Ube2g2 to allosterically enhance its interaction with cognate E3 RING domains.
The left-handed parallel β helix (LβH) fold has recently received attention as a possible structure for the prion protein (PrP) in its misfolded state. In light of this interest, we have developed an experimental system to examine the structural requirements of the LβH fold, using a known LβH protein, UDP-N-acetylglucosamine acyltransferase (LpxA), from E. coli. We showed that the β helix can tolerate...
Mycobacterium tuberculosis, the causative agent of tuberculosis, a disease that has been plaguing humanity for centuries, has a unique cell wall composition believed to be critical for pathogenicity. Luckner et al. (2009) now describe the structure of KasA, an enzyme involved in cell wall biosynthesis.
In medium-resolution (7–10 Å) cryo-electron microscopy (cryo-EM) density maps, α helices can be identified as density rods whereas β-strand or loop regions are not as easily discerned. We are proposing a computational protein structure prediction algorithm “EM-Fold” that resolves the density rod connectivity ambiguity by placing predicted α helices into the density rods and adding missing backbone...
The number of molecules with solved three-dimensional structure but unknown function is increasing rapidly. Particularly problematic are novel folds with little detectable similarity to molecules of known function. Experimental assays can determine the functions of such molecules, but are time-consuming and expensive. Computational approaches can identify potential functional sites; however, these...
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.