Crystal structure of E. coli ZinT with one zinc-binding mode and complexed with citrate

2018 ◽  
Vol 500 (2) ◽  
pp. 139-144 ◽  
Author(s):  
Jinli Chen ◽  
Lulu Wang ◽  
Fei Shang ◽  
Yuesheng Dong ◽  
Nam-Chul Ha ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Mode ◽  
Zinc Binding ◽  
E Coli

Ruthenium(II) Complexes Bearing Thioether-Appended α- Iminopyridine Ligands: Arene Precursors Permit Access to K2-N,N and K3-N,N,S Complexes

2019 ◽  
Author(s):  
Victoria A. Ternes ◽  
Hannah A. Morgan ◽  
Austin P. Lanquist ◽  
Michael P. Murray ◽  
Bradley Wile
Keyword(s):  
Crystal Structure ◽  
Solid State ◽  
Strong Field ◽  
Active Role ◽  
Binding Mode ◽  
Phenethyl Alcohol ◽  
Ru Complexes

Herein we report the preparation of a series of Ru(II) complexes featuring alpha-iminopyridine ligands bearing thioether functionality (NNS<sup>R</sup>, where R = Me, CH<sub>2</sub>Ph, Ph). Metallation using (<i>p</i> cymene)RuCl dimer permits access to (k<sup>2</sup>-N,N)Ru complexes in which the thioether moiety remains uncoordinated. In the presence of a strong field ligand such as acetonitrile or triphenylphosphine, the p-cymene moiety is displaced, and the ligand adopts a k<sup>3</sup>-N,N,S binding mode. These complexes are characterized using a combination of solution and solid state methods, including the crystal structure of [(NNS<sup>Me</sup>)Ru(NCMe)<sub>2</sub>Cl]Cl. The k<sup>2</sup>-N,N Ru(II) complexes are shown to serve as efficient precatalysts for the oxidation of sec-phenethyl alcohol at 5 mol% loadings, using a variety of external oxidants and solvents. The complex bearing an S-Ph donor was found to be the most active of those surveyed, suggesting that the thioether donor plays an active role in catalyst speciation for this transformation.

scholarly journals Crystal structures of Ca2+–calmodulin bound to NaV C-terminal regions suggest role for EF-hand domain in binding and inactivation

2019 ◽  
Vol 116 (22) ◽  
pp. 10763-10772 ◽  
Author(s):  
Bernd R. Gardill ◽  
Ricardo E. Rivera-Acevedo ◽  
Ching-Chieh Tung ◽  
Filip Van Petegem
Keyword(s):  
Crystal Structure ◽  
Binding Sites ◽  
Binding Mode ◽  
Conformational Switch ◽  
Channel Inactivation ◽  
Dependent Inactivation ◽  
Ef Hand ◽  
Inherited Arrhythmia ◽  
A Site

Voltage-gated sodium (NaV) and calcium channels (CaV) form targets for calmodulin (CaM), which affects channel inactivation properties. A major interaction site for CaM resides in the C-terminal (CT) region, consisting of an IQ domain downstream of an EF-hand domain. We present a crystal structure of fully Ca2+-occupied CaM, bound to the CT of NaV1.5. The structure shows that the C-terminal lobe binds to a site ∼90° rotated relative to a previous site reported for an apoCaM complex with the NaV1.5 CT and for ternary complexes containing fibroblast growth factor homologous factors (FHF). We show that the binding of FHFs forces the EF-hand domain in a conformation that does not allow binding of the Ca2+-occupied C-lobe of CaM. These observations highlight the central role of the EF-hand domain in modulating the binding mode of CaM. The binding sites for Ca2+-free and Ca2+-occupied CaM contain targets for mutations linked to long-QT syndrome, a type of inherited arrhythmia. The related NaV1.4 channel has been shown to undergo Ca2+-dependent inactivation (CDI) akin to CaVs. We present a crystal structure of Ca2+/CaM bound to the NaV1.4 IQ domain, which shows a binding mode that would clash with the EF-hand domain. We postulate the relative reorientation of the EF-hand domain and the IQ domain as a possible conformational switch that underlies CDI.

scholarly journals Crystal Structure of the Streptomyces coelicolor Sortase E1 Transpeptidase Provides Insight into the Binding Mode of the Novel Class E Sorting Signal

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0167763 ◽  
Author(s):  
Michele D. Kattke ◽  
Albert H. Chan ◽  
Andrew Duong ◽  
Danielle L. Sexton ◽  
Michael R. Sawaya ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Streptomyces Coelicolor ◽  
Binding Mode ◽  
The Novel ◽  
Sorting Signal ◽  
Insight Into ◽  
Class E

scholarly journals An UBR-box from a non-N-recognin: Crystal Structure of the UBR domain of UBR6

2014 ◽  
Vol 70 (a1) ◽  
pp. C306-C306
Author(s):  
Juliana Muñoz-Escobar ◽  
Guennadi Kozlov ◽  
Jean-François Trempe ◽  
Kalle Gehring
Keyword(s):  
Crystal Structure ◽  
Ubiquitin Proteasome System ◽  
Zinc Binding ◽  
Binding Motifs ◽  
Clear Explanation ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Proteasome ◽  
Binding Pockets ◽  
F Box Protein

The degradation of many short-lived proteins in eukaryotic cells is carried out by the Ubiquitin Proteasome System. The N-end rule pathway links the half-life of proteins to the identity of its N-terminal residue, also called N-degron. Destabilizing N-degrons, are recognized by E3 ubiquitin ligases termed N-recognins. N-degrons are grouped into type 1, composed of basic residues, and type 2, composed of bulky hydrophobic residues. In mammals, four N-recognins mediate the N-end rule pathway: UBR1, UBR2, UBR4 and UBR5. These proteins share a ~70-residue zinc finger-like motif termed the Ubiquitin Recognin (UBR) box, responsible for their specificity. The mammalian genome encodes at least three more UBR-box proteins: UBR3, UBR6/FBXO11 and UBR7. However, these UBRs cannot recognize any type of N-degrons. Our lab reported the crystal structures of the UBR boxes from the human UBR1 and UBR2, rationalizing the empirical rules for the classification of type 1 N-degrons. Despite the valuable information obtained from those structures there is not a clear explanation for the no recognition of N-degrons by other UBR-box proteins. Here we report the crystal structure of the UBR-box domain from UBR6 also known as FBXO11. UBR6 is a F-box protein of the SKP1-Cullin1-F-box (SCF) ubiquitin ligase complex and does not recognize any type of N-degrons. We crystallized a 77-residue fragment of the UBR-box of UBR6 and determined its structure at 1.7 Å resolution. Unexpectedly, this domain adopts an open conformation compared to UBR1-box, without any N-degron binding pockets. Its zinc-binding residues are conserved as in the N-recognins, but they are arranged in different zinc-binding motifs. Molecules form dimmers stabilized by zinc ions. The crystal had 4 molecules per asymmetric unit and space group P212121. For phasing we used Zn-SAD. With this structure we hope to obtain clues that explain the absence of N-degron recognition in some members of the UBR family.

scholarly journals Mechanism of action and NAD+-binding mode revealed by the crystal structure of L-histidinol dehydrogenase

2002 ◽  
Vol 99 (4) ◽  
pp. 1859-1864 ◽  
Author(s):  
J. A. R. G. Barbosa ◽  
J. Sivaraman ◽  
Y. Li ◽  
R. Larocque ◽  
A. Matte ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mechanism Of Action ◽  
Binding Mode ◽  
Histidinol Dehydrogenase

scholarly journals Crystal Structure ofDeinococcus radioduransRecQ Helicase Catalytic Core Domain: The Interdomain Flexibility

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sheng-Chia Chen ◽  
Chi-Hung Huang ◽  
Chia Shin Yang ◽  
Tzong-Der Way ◽  
Ming-Chung Chang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Deinococcus Radiodurans ◽  
Domain Architecture ◽  
Genome Integrity ◽  
Catalytic Core Domain ◽  
Catalytic Core ◽  
Core Domain ◽  
Winged Helix ◽  
Dna Helicases ◽  
E Coli

RecQ DNA helicases are key enzymes in the maintenance of genome integrity, and they have functions in DNA replication, recombination, and repair. In contrast to most RecQs, RecQ fromDeinococcus radiodurans(DrRecQ) possesses an unusual domain architecture that is crucial for its remarkable ability to repair DNA. Here, we determined the crystal structures of the DrRecQ helicase catalytic core and its ADP-bound form, revealing interdomain flexibility in its first RecA-like and winged-helix (WH) domains. Additionally, the WH domain of DrRecQ is positioned in a different orientation from that of theE. coliRecQ (EcRecQ). These results suggest that the orientation of the protein during DNA-binding is significantly different when comparing DrRecQ and EcRecQ.

scholarly journals Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation

2018 ◽  
Vol 116 (2) ◽  
pp. 528-533 ◽  
Author(s):  
Ivan B. Lomakin ◽  
Sergey E. Dmitriev ◽  
Thomas A. Steitz
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Translation Initiation ◽  
Zinc Ion ◽  
Zinc Binding ◽  
Ion Binding ◽  
Binding Interface ◽  
Zinc Binding Site ◽  
Reading Frames ◽  
Zinc Ion Binding

The density-regulated protein (DENR) and the malignant T cell-amplified sequence 1 (MCT-1/MCTS1) oncoprotein support noncanonical translation initiation, promote translation reinitiation on a specific set of mRNAs with short upstream reading frames, and regulate ribosome recycling. DENR and MCT-1 form a heterodimer, which binds to the ribosome. We determined the crystal structure of the heterodimer formed by human MCT-1 and the N-terminal domain of DENR at 2.0-Å resolution. The structure of the heterodimer reveals atomic details of the mechanism of DENR and MCT-1 interaction. Four conserved cysteine residues of DENR (C34, C37, C44, C53) form a classical tetrahedral zinc ion-binding site, which preserves the structure of the DENR’s MCT-1–binding interface that is essential for the dimerization. Substitution of all four cysteines by alanine abolished a heterodimer formation. Our findings elucidate further the mechanism of regulation of DENR-MCT-1 activities in unconventional translation initiation, reinitiation, and recycling.

scholarly journals Cyclic Boronates Inhibit All Classes of β-Lactamases

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Samuel T. Cahill ◽  
Ricky Cain ◽  
David Y. Wang ◽  
Christopher T. Lohans ◽  
David W. Wareham ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Bacterial Infections ◽  
Binding Mode ◽  
Gram Negative ◽  
Content Type ◽  
Class A ◽  
Class D ◽  
Dual Action ◽  
The Common ◽  
Continued Use

ABSTRACT β-Lactamase-mediated resistance is a growing threat to the continued use of β-lactam antibiotics. The use of the β-lactam-based serine-β-lactamase (SBL) inhibitors clavulanic acid, sulbactam, and tazobactam and, more recently, the non-β-lactam inhibitor avibactam has extended the utility of β-lactams against bacterial infections demonstrating resistance via these enzymes. These molecules are, however, ineffective against the metallo-β-lactamases (MBLs), which catalyze their hydrolysis. To date, there are no clinically available metallo-β-lactamase inhibitors. Coproduction of MBLs and SBLs in resistant infections is thus of major clinical concern. The development of “dual-action” inhibitors, targeting both SBLs and MBLs, is of interest, but this is considered difficult to achieve due to the structural and mechanistic differences between the two enzyme classes. We recently reported evidence that cyclic boronates can inhibit both serine- and metallo-β-lactamases. Here we report that cyclic boronates are able to inhibit all four classes of β-lactamase, including the class A extended spectrum β-lactamase CTX-M-15, the class C enzyme AmpC from Pseudomonas aeruginosa, and class D OXA enzymes with carbapenem-hydrolyzing capabilities. We demonstrate that cyclic boronates can potentiate the use of β-lactams against Gram-negative clinical isolates expressing a variety of β-lactamases. Comparison of a crystal structure of a CTX-M-15:cyclic boronate complex with structures of cyclic boronates complexed with other β-lactamases reveals remarkable conservation of the small-molecule binding mode, supporting our proposal that these molecules work by mimicking the common tetrahedral anionic intermediate present in both serine- and metallo-β-lactamase catalysis.

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