scholarly journals Structural Features, Biological Functions of the Alpha-1 Antitrypsin and Contribution to Esophageal Cancer

10.5772/30476 ◽  
2012 ◽  
Author(s):  
Shahla Mohammad ◽  
Ferdous Rastgar ◽  
Abbas Sahebghadam-Lotfi
Keyword(s):  
Esophageal Cancer ◽  
Structural Features ◽  
Biological Functions ◽  
Alpha 1 Antitrypsin

scholarly journals Post-Translational Modifications of Circulating Alpha-1-Antitrypsin Protein

2020 ◽  
Vol 21 (23) ◽  
pp. 9187
Author(s):  
Urszula Lechowicz ◽  
Stefan Rudzinski ◽  
Aleksandra Jezela-Stanek ◽  
Sabina Janciauskiene ◽  
Joanna Chorostowska-Wynimko
Keyword(s):  
Acute Phase Protein ◽  
Molecular Forms ◽  
Biological Functions ◽  
Post Translational Modifications ◽  
Serpina1 Gene ◽  
Phase Protein ◽  
Other Substances ◽  
Alpha 1 Antitrypsin ◽  
And Function ◽  
Antiprotease Activity

Alpha-1-antitrypsin (AAT), an acute-phase protein encoded by the SERPINA1 gene, is a member of the serine protease inhibitor (SERPIN) superfamily. Its primary function is to protect tissues from enzymes released during inflammation, such as neutrophil elastase and proteinase 3. In addition to its antiprotease activity, AAT interacts with numerous other substances and has various functions, mainly arising from the conformational flexibility of normal variants of AAT. Therefore, AAT has diverse biological functions and plays a role in various pathophysiological processes. This review discusses major molecular forms of AAT, including complex, cleaved, glycosylated, oxidized, and S-nitrosylated forms, in terms of their origin and function.

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.

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 Identification and Changes in the Seasonal Concentrations of Proteins Regulating the Biological Functions of Spermatozoa and Participating in Their Cytoskeleton Organization in Roe Deer (Capreolus Capreolus) Epididymides

2018 ◽  
Vol 18 (2) ◽  
pp. 417-428
Author(s):  
Anna M. Majewska ◽  
Marek Lecewicz ◽  
Władysław Kordan ◽  
Paweł Wysocki
Keyword(s):  
Roe Deer ◽  
Capreolus Capreolus ◽  
Reproductive Season ◽  
Sperm Maturation ◽  
Maturation Process ◽  
Biological Functions ◽  
Cytoskeleton Organization ◽  
Tissue Homogenates ◽  
Alpha 1 Antitrypsin ◽  
Almost All

Abstract In the case of animals characterized by a strongly marked seasonality of reproduction, extremely significant seem to be periodical fluctuations in the concentration of proteinaceous substances identified in tissues and fluids of epididymides, which take part in the maturation process of sperm cells. The aim of the present study was to compare the seasonal expression of identified proteins present in various regions of the mature roe deer (Capreolus capreolus) epididymides, which are regulating the biological functions of spermatozoa and participating in their cytoskeleton organization during the sperm maturation process. Epididymal tissue homogenates and epididymal fluids were analyzed by two-dimensional electrophoresis (2D-PAGE) and tandem mass spectrometry (MS/MS) to reveal 31 polypeptides with different biochemical functions. Moreover, among the identified polypeptides, twelve of them were similar to: alpha-enolase isoform 3; endoplasmic reticulum resident protein 29; calreticulin, calponin-1 isoform X1; transgelin; vimentin; tubulin; desmin; tropomyosin; actin; alpha-1 antitrypsin isoform X1 and 14-3-3 protein epsilon. Concentrations of the analyzed polypeptides, expressed in optical density units (ODU), differed significantly (P≤0.05) across the examined periods of the reproductive season. The highest ODU values of almost all analyzed proteins were observed during the rutting period. This variation in the identified proteins in the epididymal tissues and fluids of roe deer throughout the reproductive season could be indicative of their important roles in sperm maturation within the epididymis.

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.

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
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