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Article
Open AccessChemical manipulation of an activation/inhibition switch in the nuclear receptor PXR
Nuclear receptors are ligand-activated transcription factors that can often be useful drug targets. Unfortunately, ligand promiscuity leads to two-thirds of receptors remaining clinically untargeted. PXR is a ...
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Article
Open AccessStructural basis of BAK activation in mitochondrial apoptosis initiation
BCL-2 proteins regulate mitochondrial poration in apoptosis initiation. How the pore-forming BCL-2 Effector BAK is activated remains incompletely understood mechanistically. Here we investigate autoactivation ...
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Article
Expression system for structural and functional studies of human glycosylation enzymes
A modular protein expression system enables the structural and functional characterization of human glycosyltransferases, glycoside hydrolases and other carbohydrate-modifying enzymes. ...
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Article
Open AccessMolecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase
Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) play a central role in tryptophan metabolism and are involved in many cellular and disease processes. Here we report the crystal structure...
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Article
Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations
The first structures of the mammalian phosphofructokinase-1 tetramer are reported, for the human platelet isoform, in complex with ATP–Mg2+ and ADP.
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Article
Design of activated serine–containing catalytic triads with atomic-level accuracy
De novo enzyme designs have generally tried to optimize multiple aspects of enzyme function simultaneously. Focusing only on positioning of active site residues to generate a nucleophilic serine as assessed by ac...
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Article
Two Fe-S clusters catalyze sulfur insertion by radical-SAM methylthiotransferases
Methylthiolation by radical SAM enzymes is thought to include the sacrificial breakdown of a second Fe-S cluster to generate the sulfur cosubstrate. A biochemical, spectroscopic and structural study of two met...
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Article
Solution NMR and X-ray crystal structures of Pseudomonas syringae Pspto_3016 from protein domain family PF04237 (DUF419) adopt a “double wing” DNA binding motif
The protein Pspto_3016 is a 117-residue member of the protein domain family PF04237 (DUF419), which is to date a functionally uncharacterized family of proteins. In this report, we describe the structure of Ps...
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Article
Crystal structure of a catalytically active GG(D/E)EF diguanylate cyclase domain from Marinobacter aquaeolei with bound c-di-GMP product
Recent studies of signal transduction in bacteria have revealed a unique second messenger, bis-(3′–5′)-cyclic dimeric GMP (c-di-GMP), which regulates transitions between motile states and sessile states, such ...
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Article
Three structural representatives of the PF06855 protein domain family from Staphyloccocus aureus and Bacillus subtilis have SAM domain-like folds and different functions
Protein domain family PF06855 (DUF1250) is a family of small domains of unknown function found only in bacteria, and mostly in the order Bacillales and Lactobacillales. Here we describe the solution NMR or X-ray ...
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Article
UNC119 is required for G protein trafficking in sensory neurons
UNC119 is a protein localized to the non-motile primary cilia. Here, Zhang et al. report the crystal structure of UNC119 and provide biochemical and cellular evidence that UNC119 is a lipid-binding protein that m...
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Article
NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan UFM1-UBA5-UFC1 ubiquination pathway
For cell regulation, E2-like ubiquitin-fold modifier conjugating enzyme 1 (Ufc1) is involved in the transfer of ubiquitin-fold modifier 1 (Ufm1), a ubiquitin like protein which is activated by E1-like enzyme U...
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Article
Functional insights from structural genomics
Structural genomics efforts have produced structural information, either directly or by modeling, for thousands of proteins over the past few years. While many of these proteins have known functions, a large p...