scholarly journals Crystal Structure of Nitrilase-Like Protein Nit2 from Kluyveromyces lactis

Crystals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 499
Author(s):  
Chaewon Jin ◽  
Hyeonseok Jin ◽  
Byung-Cheon Jeong ◽  
Dong-Hyung Cho ◽  
Hang-Suk Chun ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Posttranslational Modifications ◽  
Tumor Suppressors ◽  
Kluyveromyces Lactis ◽  
Structural Features ◽  
Biological Functions ◽  
Repair Enzyme ◽  
Amidase Activity ◽  
Structural Relationships ◽  
Metabolite Repair

The nitrilase superfamily, including 13 branches, plays various biological functions in signaling molecule synthesis, vitamin metabolism, small-molecule detoxification, and posttranslational modifications. Most of the mammals and yeasts have Nit1 and Nit2 proteins, which belong to the nitrilase-like (Nit) branch of the nitrilase superfamily. Recent studies have suggested that Nit1 is a metabolite repair enzyme, whereas Nit2 shows ω-amidase activity. In addition, Nit1 and Nit2 are suggested as putative tumor suppressors through different ways in mammals. Yeast Nit2 (yNit2) is a homolog of mouse Nit1 based on similarity in sequence. To understand its specific structural features, we determined the crystal structure of Nit2 from Kluyveromyces lactis (KlNit2) at 2.2 Å resolution and compared it with the structure of yeast-, worm-, and mouse-derived Nit2 proteins. Based on our structural analysis, we identified five distinguishable structural features from 28 structural homologs. This study might potentially provide insights into the structural relationships of a broad spectrum of nitrilases.

Plant nitrilase: a new job for an old enzyme

2019 ◽  
Vol 476 (7) ◽  
pp. 1105-1107
Author(s):  
Joseph M. Jez
Keyword(s):  
Arabidopsis Thaliana ◽  
Recent Work ◽  
Carboxylic Acids ◽  
Auxin Biosynthesis ◽  
Biological Functions ◽  
Repair Enzyme ◽  
Biochemical Journal ◽  
Metabolite Repair

Abstract Nitrilases are versatile enzymes that hydrolyze nitriles to carboxylic acids and ammonia, but many members of this family lack defined biological functions. In plants, nitrilases have been associated with detoxification of cyanide-containing compounds and auxin biosynthesis; however, recent work suggests that the chemical versatility of these proteins contributes to metabolite repair. In this issue of the Biochemical Journal, Niehaus et al. demonstrate that the Nit1 nitrilase from Arabidopsis thaliana functions as a metabolite repair enzyme that removes deaminated glutathione from the cytoplasm and plastids.

scholarly journals DAXX in cancer: phenomena, processes, mechanisms and regulation

2019 ◽  
Vol 47 (15) ◽  
pp. 7734-7752 ◽  
Author(s):  
Iqbal Mahmud ◽  
Daiqing Liao
Keyword(s):  
Posttranslational Modifications ◽  
Treatment Resistance ◽  
Structural Features ◽  
Nuclear Bodies ◽  
Biological Functions ◽  
Chromatin Remodelers ◽  
Pml Nuclear Bodies ◽  
Epigenetic Modifiers ◽  
Complex Functions ◽  
Key Events

AbstractDAXX displays complex biological functions. Remarkably, DAXX overexpression is a common feature in diverse cancers, which correlates with tumorigenesis, disease progression and treatment resistance. Structurally, DAXX is modular with an N-terminal helical bundle, a docking site for many DAXX interactors (e.g. p53 and ATRX). DAXX’s central region folds with the H3.3/H4 dimer, providing a H3.3-specific chaperoning function. DAXX has two functionally critical SUMO-interacting motifs. These modules are connected by disordered regions. DAXX’s structural features provide a framework for deciphering how DAXX mechanistically imparts its functions and how its activity is regulated. DAXX modulates transcription through binding to transcription factors, epigenetic modifiers, and chromatin remodelers. DAXX’s localization in the PML nuclear bodies also plays roles in transcriptional regulation. DAXX-regulated genes are likely important effectors of its biological functions. Deposition of H3.3 and its interactions with epigenetic modifiers are likely key events for DAXX to regulate transcription, DNA repair, and viral infection. Interactions between DAXX and its partners directly impact apoptosis and cell signaling. DAXX’s activity is regulated by posttranslational modifications and ubiquitin-dependent degradation. Notably, the tumor suppressor SPOP promotes DAXX degradation in phase-separated droplets. We summarize here our current understanding of DAXX’s complex functions with a focus on how it promotes oncogenesis.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

scholarly journals The crystal structure of the first ether solvate of hexaphenyldistannane [(Ph3Sn)2 • 2 THF]

2020 ◽  
Vol 43 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Jonathan O. Bauer
Keyword(s):  
Crystal Structure ◽  
Inclusion Compounds ◽  
Molecular Crystal ◽  
Structural Features ◽  
Structural Investigations ◽  
Crystal Solvates

AbstractStructural investigations of molecular crystal solvates can provide important information for the targeted crystallization of particular inclusion compounds. Here, the crystal structure of the first ether solvate of hexaphenyldistannane [(Ph3Sn)2 • 2 THF] is reported. Structural features in terms of host-guest interactions and in the context of the previously reported polymorphs and solvates of (Ph3Sn)2 are discussed.

scholarly journals Crystal structure of a new lithium iron vanadate

2014 ◽  
Vol 70 (a1) ◽  
pp. C1101-C1101
Author(s):  
Laurent Castro ◽  
Nicolas Penin ◽  
Dany Carlier ◽  
Alain Wattiaux ◽  
Stanislav Pechev ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Room Temperature ◽  
Magnetic Measurements ◽  
Charge Compensation ◽  
Li Ion Batteries ◽  
New Materials ◽  
Single Crystal Diffraction ◽  
Structural Relationships ◽  
Network Flexibility ◽  
Li Ion

Iron vanadates and phosphates have been widely explored [1-2] as possible electrode material for Li-ion batteries. In the goal of finding new materials, our approach was to consider existing materials and to investigate the flexibility of their network for possible substitutions. Among the different materials containing iron and vanadium, Cu3Fe4(XO4)6 (X = P, V) are isostructural to Fe7(PO4)6. Lafontaine et al. [3] discussed the structural relationships between β-Cu3Fe4(VO4)6 and several other vanadates, phosphates and molybdates of general formula AxBy(VO4)6. The interesting network flexibility was then demonstrated with the existence of four different crystallographic sites, which can be partially occupied depending on the x+y value : x+y = 7 for β-Cu3Fe4(VO4)6) and x+y = 8 for NaCuFe2(VO4)3. The LixFey(VO4)6 phase was then prepared considering the substitution of Li+ and Fe3+ for Cu2+ ions in β-Cu3Fe4(VO4)6 and the existence of an extra site to accommodate the charge compensation (7 ≤ x+y ≤ 8). As expected, a new lithium iron vanadate, isotructural to mineral Howardevansite was then obtained. Single crystal diffraction data were collected at room temperature on Enraf-Nonius CAD-4 diffractometer. Structure was refined with JANA-2006 program package. Mössbauer and magnetic measurements were also used to check the oxidation state of iron ions, to support the obtained crystal structure and to consider any possible structural/magnetic transitions. All the results will be presented and discussed in this presentation.

Structural insights into dihydroxylation of terephthalate, a product of polyethylene terephthalate degradation

2022 ◽  
Author(s):  
Jai Krishna Mahto ◽  
Neetu Neetu ◽  
Monica Sharma ◽  
Monika Dubey ◽  
Bhanu Prakash Vellanki ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Substrate Specificity ◽  
Polyethylene Terephthalate ◽  
Active Site ◽  
Catalytic Domain ◽  
Structural Features ◽  
Comamonas Testosteroni ◽  
Plastic Pollution ◽  
Microbial Utilization ◽  
Steady State Kinetics

Biodegradation of terephthalate (TPA) is a highly desired catabolic process for the bacterial utilization of this Polyethylene terephthalate (PET) depolymerization product, but to date, the structure of terephthalate dioxygenase (TPDO), a Rieske oxygenase (RO) that catalyzes the dihydroxylation of TPA to a cis -diol is unavailable. In this study, we characterized the steady-state kinetics and first crystal structure of TPDO from Comamonas testosteroni KF1 (TPDO KF1 ). The TPDO KF1 exhibited the substrate specificity for TPA ( k cat / K m = 57 ± 9 mM −1 s −1 ). The TPDO KF1 structure harbors characteristics RO features as well as a unique catalytic domain that rationalizes the enzyme’s function. The docking and mutagenesis studies reveal that its substrate specificity to TPA is mediated by Arg309 and Arg390 residues, two residues positioned on opposite faces of the active site. Additionally, residue Gln300 is also proven to be crucial for the activity, its substitution to alanine decreases the activity ( k cat ) by 80%. Together, this study delineates the structural features that dictate the substrate recognition and specificity of TPDO. Importance The global plastic pollution has become the most pressing environmental issue. Recent studies on enzymes depolymerizing polyethylene terephthalate plastic into terephthalate (TPA) show some potential in tackling this. Microbial utilization of this released product, TPA is an emerging and promising strategy for waste-to-value creation. Research from the last decade has discovered terephthalate dioxygenase (TPDO), as being responsible for initiating the enzymatic degradation of TPA in a few Gram-negative and Gram-positive bacteria. Here, we have determined the crystal structure of TPDO from Comamonas testosteroni KF1 and revealed that it possesses a unique catalytic domain featuring two basic residues in the active site to recognize TPA. Biochemical and mutagenesis studies demonstrated the crucial residues responsible for the substrate specificity of this enzyme.

Peroxisomal multifunctional enzyme type 2 from the fruitfly: dehydrogenase and hydratase act as separate entities, as revealed by structure and kinetics

2011 ◽  
Vol 435 (3) ◽  
pp. 771-781 ◽  
Author(s):  
Tatu J. K. Haataja ◽  
M. Kristian Koski ◽  
J. Kalervo Hiltunen ◽  
Tuomo Glumoff
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Drosophila Melanogaster ◽  
Structural Features ◽  
Full Length ◽  
Multifunctional Enzyme ◽  
Domain Composition ◽  
Substrate Channelling

All of the peroxisomal β-oxidation pathways characterized thus far house at least one MFE (multifunctional enzyme) catalysing two out of four reactions of the spiral. MFE type 2 proteins from various species display great variation in domain composition and predicted substrate preference. The gene CG3415 encodes for Drosophila melanogaster MFE-2 (DmMFE-2), complements the Saccharomyces cerevisiae MFE-2 deletion strain, and the recombinant protein displays both MFE-2 enzymatic activities in vitro. The resolved crystal structure is the first one for a full-length MFE-2 revealing the assembly of domains, and the data can also be transferred to structure–function studies for other MFE-2 proteins. The structure explains the necessity of dimerization. The lack of substrate channelling is proposed based on both the structural features, as well as by the fact that hydration and dehydrogenation activities of MFE-2, if produced as separate enzymes, are equally efficient in catalysis as the full-length MFE-2.

Crystal Structure of Human Dual-Specificity Tyrosine-Regulated Kinase 3 Reveals New Structural Features and Insights into its Auto-phosphorylation

2018 ◽  
Vol 430 (10) ◽  
pp. 1521-1530 ◽  
Author(s):  
Kuglae Kim ◽  
Jeong Seok Cha ◽  
Yong-Soon Cho ◽  
Hoyoung Kim ◽  
Nienping Chang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Structural Features ◽  
Dual Specificity
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