scholarly journals The Plant Peptidome: An Expanding Repertoire of Structural Features and Biological Functions

2015 ◽  
Vol 27 (8) ◽  
pp. 2095-2118 ◽  
Author(s):  
Patrizia Tavormina ◽  
Barbara De Coninck ◽  
Natalia Nikonorova ◽  
Ive De Smet ◽  
Bruno P.A. Cammue
Keyword(s):  
Structural Features ◽  
Biological Functions

scholarly journals Correlation of Fragile Histidine Triad (Fhit) Protein Structural Features with Effector Interactions and Biological Functions

2008 ◽  
Vol 284 (2) ◽  
pp. 1040-1049 ◽  
Author(s):  
Flavia Pichiorri ◽  
Hiroshi Okumura ◽  
Tatsuya Nakamura ◽  
Preston N. Garrison ◽  
Pierluigi Gasparini ◽  
...  
Keyword(s):  
Structural Features ◽  
Biological Functions ◽  
Fragile Histidine Triad ◽  
Fhit Protein

scholarly journals Unique structural features of the mitochondrial AAA+ protease AFG3L2 reveal the molecular basis for activity in health and disease

2019 ◽  
Author(s):  
Cristina Puchades ◽  
Bojian Ding ◽  
Albert Song ◽  
R. Luke Wiseman ◽  
Gabriel C. Lander ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Structural Data ◽  
Structural Features ◽  
Genetic Mutations ◽  
Biological Functions ◽  
Catalytic Core ◽  
Structural Framework ◽  
Health And Disease

AbstractMitochondrial AAA+ quality control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying molecular mechanisms that define the diverse activities of these enzymes remain poorly defined. The mitochondrial AAA+ protease AFG3L2 is of particular interest, as genetic mutations localized throughout AFG3L2 are linked to diverse neurodegenerative disorders. However, a lack of structural data has limited our understanding of how mutations impact enzymatic activity. Here, we used cryo-EM to determine a substrate-bound structure of the catalytic core of human AFG3L2. This structure identifies multiple specialized structural features within AFG3L2 that integrate with conserved structural motifs required for hand-over-hand ATP-dependent substrate translocation to engage, unfold and degrade targeted proteins. Mapping disease-relevant AFG3L2 mutations onto our structure demonstrates that many of these mutations localize to these unique structural features of AFG3L2 and distinctly influence its activity and stability. Our results provide a molecular basis for neurological phenotypes associated with different AFG3L2 mutations, and establish a structural framework to understand how different members of the AAA+ superfamily achieve specialized, diverse biological functions.

scholarly journals Recent advances in small molecular modulators targeting histone deacetylase 6

2020 ◽  
Vol 2 (4) ◽  
pp. FDD53
Author(s):  
Yufeng Xiao ◽  
Xuan Zhang
Keyword(s):  
Drug Design ◽  
Histone Deacetylase ◽  
Neurological Disorders ◽  
Therapeutic Strategy ◽  
Structural Features ◽  
Biological Functions ◽  
Histone Deacetylase 6 ◽  
Selective Inhibitors ◽  
Recent Advances

Histone deacetylase 6 (HDAC6) is a unique isozyme in the HDAC family with various distinguished characters. HDAC6 is predominantly localized in the cytoplasm and has several specific nonhistone substrates, such as α-tubulin, cortactin, Hsp90, tau and peroxiredoxins. Accumulating evidence reveals that targeting HDAC6 may serve as a promising therapeutic strategy for the treatment of cancers, neurological disorders and immune diseases, making the development of HDAC6 inhibitors particularly attractive. Recently, multitarget drug design and proteolysis targeting chimera technology have also been applied in the discovery of novel small molecular modulators targeting HDAC6. In this review, we briefly describe the structural features and biological functions of HDAC6 and discuss the recent advances in HDAC6 modulators, including selective inhibitors, chimeric inhibitors and proteolysis targeting chimeras for multiple therapeutic purposes.

scholarly journals MARTs and MARylation in the Cytosol: Biological Functions, Mechanisms of Action, and Therapeutic Potential

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 313
Author(s):  
Sridevi Challa ◽  
MiKayla S. Stokes ◽  
W. Lee Kraus
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
New Technologies ◽  
Therapeutic Potential ◽  
Structural Features ◽  
Cellular Transport ◽  
Biological Functions ◽  
Post Translational Modification

Mono(ADP-ribosyl)ation (MARylation) is a regulatory post-translational modification of proteins that controls their functions through a variety of mechanisms. MARylation is catalyzed by mono(ADP-ribosyl) transferase (MART) enzymes, a subclass of the poly(ADP-ribosyl) polymerase (PARP) family of enzymes. Although the role of PARPs and poly(ADP-ribosyl)ation (PARylation) in cellular pathways, such as DNA repair and transcription, is well studied, the role of MARylation and MARTs (i.e., the PARP ‘monoenzymes’) are not well understood. Moreover, compared to PARPs, the development of MART-targeted therapeutics is in its infancy. Recent studies are beginning to shed light on the structural features, catalytic targets, and biological functions of MARTs. The development of new technologies to study MARTs have uncovered essential roles for these enzymes in the regulation of cellular processes, such as RNA metabolism, cellular transport, focal adhesion, and stress responses. These insights have increased our understanding of the biological functions of MARTs in cancers, neuronal development, and immune responses. Furthermore, several novel inhibitors of MARTs have been developed and are nearing clinical utility. In this review, we summarize the biological functions and molecular mechanisms of MARTs and MARylation, as well as recent advances in technology that have enabled detection and inhibition of their activity. We emphasize PARP-7, which is at the forefront of the MART subfamily with respect to understanding its biological roles and the development of therapeutically useful inhibitors. Collectively, the available studies reveal a growing understanding of the biochemistry, chemical biology, physiology, and pathology of MARTs.

scholarly journals Proton-Sensing GPCRs in Health and Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2050
Author(s):  
Marco Sisignano ◽  
Michael J. M. Fischer ◽  
Gerd Geisslinger
Keyword(s):  
Intestinal Inflammation ◽  
Tumor Biology ◽  
Structural Features ◽  
G Protein Coupled Receptors ◽  
Biological Functions ◽  
Future Studies ◽  
Health And Disease ◽  
G Protein Coupled ◽  
Potential Use

The group of proton-sensing G-protein coupled receptors (GPCRs) consists of the four receptors GPR4, TDAG8 (GPR65), OGR1 (GPR68), and G2A (GPR132). These receptors are cellular sensors of acidification, a property that has been attributed to the presence of crucial histidine residues. However, the pH detection varies considerably among the group of proton-sensing GPCRs and ranges from pH of 5.5 to 7.8. While the proton-sensing GPCRs were initially considered to detect acidic cellular environments in the context of inflammation, recent observations have expanded our knowledge about their physiological and pathophysiological functions and many additional individual and unique features have been discovered that suggest a more differentiated role of these receptors in health and disease. It is known that all four receptors contribute to different aspects of tumor biology, cardiovascular physiology, and asthma. However, apart from their overlapping functions, they seem to have individual properties, and recent publications identify potential roles of individual GPCRs in mechanosensation, intestinal inflammation, oncoimmunological interactions, hematopoiesis, as well as inflammatory and neuropathic pain. Here, we put together the knowledge about the biological functions and structural features of the four proton-sensing GPCRs and discuss the biological role of each of the four receptors individually. We explore all currently known pharmacological modulators of the four receptors and highlight potential use. Finally, we point out knowledge gaps in the biological and pharmacological context of proton-sensing GPCRs that should be addressed by future studies.

Notes: Structural Features and Biological Functions in Blue Copper Proteins

1987 ◽  
Vol 42 (11-12) ◽  
pp. 1358-1360 ◽  
Author(s):  
Yuzo Nishida
Keyword(s):  
Electron Transfer ◽  
Unpaired Electron ◽  
Structural Features ◽  
Copper Proteins ◽  
Blue Copper Proteins ◽  
Biological Functions ◽  
Electron Carrier ◽  
Blue Copper ◽  
Redox Partners

A new idea that elucidates the electron carrier ability of plastocyanin (and of azurin) is proposed. It emphasizes the fact that two lobes of the d-orbital, where one unpaired electron of copper (II) ion lies, are not screened by the ligand atoms, which would facilitate the electron transfer between the d-orbital and the redox partners (cytochrom f and P-700 in the case of plastocyanin). Several evidences which support the above proposal are provided.

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.

scholarly journals Novel Fission Yeast Cdc7-Dbf4-Like Kinase Complex Required for the Initiation and Progression of Meiotic Second Division

2002 ◽  
Vol 22 (1) ◽  
pp. 309-320 ◽  
Author(s):  
Taro Nakamura ◽  
Michiko Nakamura-Kubo ◽  
Tomohiro Nakamura ◽  
Chikashi Shimoda
Keyword(s):  
Dna Replication ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Structural Features ◽  
Regulatory Subunit ◽  
Primary Role ◽  
Biological Functions ◽  
Cdc7 Kinase ◽  
Initiation Of Dna Replication ◽  
Novel Protein

ABSTRACT Cdc7, a conserved serine/threonine protein kinase, controls initiation of DNA replication. A regulatory subunit, Dbf4, stimulates the kinase activity of Cdc7 and recruits it to the replication origins. Schizosaccharomyces pombe has a homologous kinase complex, composed of Hsk1 and Dfp1/Him1. Here, we report a novel protein kinase of S. pombe, Spo4, which shares common structural features with the Cdc7 kinases. In spite of the structural similarities, Spo4 is dispensable for mitotic growth and premeiotic DNA replication. Intriguingly, spo4 null mutants are defective in initiation and progression of the second meiotic division. Spindles for meiosis II are often fragmented. Spo4 kinase activity is markedly enhanced when the enzyme is associated with its regulatory subunit, Spo6, a Dbf4-like protein. Expression of Spo4 is specifically induced during meiosis. Spo4 is preferentially present in nuclei, but this nuclear localization does not require Spo6. These results suggest that Spo4 is a Cdc7 kinase whose primary role is in meiosis, not in DNA replication. This is the first report of an organism which has two Cdc7-related kinase complexes with different biological functions.

Vismodegib anticancer drug: Analyzing electronic and structural features and examining biological activities

2021 ◽  
pp. 1-10
Author(s):  
Tahereh Mohseniabbasabadi ◽  
Farnoosh Behboodyzad ◽  
Firoozeh Abolhasani Zadeh ◽  
Ebrahim Balali
Keyword(s):  
Anticancer Drug ◽  
Biological Activities ◽  
Dominant Role ◽  
Structural Features ◽  
Biological Functions ◽  
Docking Simulations ◽  
Halogen Atoms ◽  
Other Substances ◽  
Better Than

Vismodegib (Vis) is an anticancer drug, in which its electronic and structural features were examined in this work. To this aim, the chlorine atoms of original Vis model were substituted by other fluorine, bromine, and iodine halogen atoms yielding F-Vis, Br-Vis, and I-Vis in addition to the original Cl-Vis model. The models were optimized by performing quantum chemical calculations and their interactions with the smoothened (SMO) target were examined by performing molecular docking simulations. The results indicated that the stabilized structures of halogenated Vis models were achievable and their features indicated the dominant role of halogen atoms for their participation in interactions with other substances. Based on the obtained results, Br-Vis model was seen suitable for participating in interaction with the SMO target even better than the original Vis model. The hypothesis of this work was affirmed by employing the in silico approach for analyzing the features of singular ligands and for evaluating their biological functions.

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