UDP-glucose dehydrogenase: structure and function of a potential drug target

2010 ◽  
Vol 38 (5) ◽  
pp. 1378-1385 ◽  
Author(s):  
Sigrid Egger ◽  
Apirat Chaikuad ◽  
Kathryn L. Kavanagh ◽  
Udo Oppermann ◽  
Bernd Nidetzky
Keyword(s):  
Sequence Comparison ◽  
Drug Target ◽  
Glucuronic Acid ◽  
Glucose Dehydrogenase ◽  
Enzymatic Reaction ◽  
Cysteine Residue ◽  
Structure And Function ◽  
Eukaryotic Group ◽  
And Function ◽  
Covalent Catalysis

Biosynthesis of the glycosaminoglycan precursor UDP-α-D-glucuronic acid occurs through a 2-fold oxidation of UDP-α-D-glucose that is catalysed by UGDH (UDP-α-D-glucose 6-dehydrogenase). Structure–function relationships for UGDH and proposals for the enzymatic reaction mechanism are reviewed in the present paper, and structure-based sequence comparison is used for subclassification of UGDH family members. The eukaryotic group of enzymes (UGDH-II) utilize an extended C-terminal domain for the formation of complex homohexameric assemblies. The comparably simpler oligomerization behaviour of the prokaryotic group of enzymes (UGDH-I), in which dimeric forms prevail, is traced back to the lack of relevant intersubunit contacts and trimmings within the C-terminal region. The active site of UGDH contains a highly conserved cysteine residue, which plays a key role in covalent catalysis. Elevated glycosaminoglycan formation is implicated in a variety of human diseases, including the progression of tumours. The inhibition of synthesis of UDP-α-D-glucuronic acid using UGDH antagonists might therefore be a useful strategy for therapy.

scholarly journals UDP-Glucose Dehydrogenases: Identification, Expression, and Function Analyses in Upland Cotton (Gossypium hirsutum)

2021 ◽  
Vol 11 ◽  
Author(s):  
Tingting Jia ◽  
Qun Ge ◽  
Shuya Zhang ◽  
Zhen Zhang ◽  
Aiying Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Upland Cotton ◽  
Plant Cell Wall ◽  
Glucuronic Acid ◽  
Glucose Dehydrogenase ◽  
Fiber Development ◽  
Protein Domain ◽  
Cell Wall Synthesis ◽  
Wild Type ◽  
And Function

UDP-glucose dehydrogenase (UGD; EC1.1.1.22) is a NAD+-dependent enzyme that catalyzes the two-fold oxidation of UDP-glucose (UDP-Glc) to produce UDP-glucuronic acid and plays an important role in plant cell wall synthesis. A total of 42 UGD genes from four Gossypium genomes including G. hirsutum, G. arboretum, G. barbadense, and G. raimondii were identified and found that the UGD gene family has conservative evolution patterns in gene structure and protein domain. The growth of fibers can be effectively promoted after adding the UDP-Glc to the medium, and the GhUGD gene expression enhanced. In addition, the transgenic Arabidopsis lines over-expressing GH_D12G1806 had longer root lengths and higher gene expression level than the wild-type plants of Columbia-0. These results indicated that UGD may play important roles in cotton fiber development and has a guiding significance for dissecting fiber development mechanism.

scholarly journals Current understanding of thalamic structure and function in migraine

Cephalalgia ◽  
2018 ◽  
Vol 39 (13) ◽  
pp. 1675-1682 ◽  
Author(s):  
Samaira Younis ◽  
Anders Hougaard ◽  
Rodrigo Noseda ◽  
Messoud Ashina
Keyword(s):  
Drug Target ◽  
Critical Role ◽  
Structure And Function ◽  
Pain Modulation ◽  
Clinical Implications ◽  
Important Position ◽  
Cortical Regions ◽  
And Function ◽  
Thalamic Structure

Objective To review and discuss the literature on the role of thalamic structure and function in migraine. Discussion The thalamus holds an important position in our understanding of allodynia, central sensitization and photophobia in migraine. Structural and functional findings suggest abnormal functional connectivity between the thalamus and various cortical regions pointing towards an altered pain processing in migraine. Pharmacological nociceptive modulation suggests that the thalamus is a potential drug target. Conclusion A critical role for the thalamus in migraine-related allodynia and photophobia is well established. Additionally, the thalamus is most likely involved in the dysfunctional pain modulation and processing in migraine, but further research is needed to clarify the exact clinical implications of these findings.

Structure and Function of Prokaryotic UDP-Glucose Pyrophosphorylase, A Drug Target Candidate

2015 ◽  
Vol 22 (14) ◽  
pp. 1687-1697 ◽  
Author(s):  
M. Berbis ◽  
Jose Sanchez-Puelles ◽  
F. Canada ◽  
Jesus Jimenez-Barbero
Keyword(s):  
Drug Target ◽  
Structure And Function ◽  
And Function

[NiFe]-Hydrogenase maturation endopeptidase: structure and function

2005 ◽  
Vol 33 (1) ◽  
pp. 108-111 ◽  
Author(s):  
E. Theodoratou ◽  
R. Huber ◽  
A. Böck
Keyword(s):  
Reaction Mechanism ◽  
Substrate Specificity ◽  
Large Subunit ◽  
Cysteine Residue ◽  
Structure And Function ◽  
Metal Centre ◽  
Conformational Switch ◽  
Hydrogenase Maturation ◽  
And Function

Hydrogenase maturation endopeptidases catalyse the terminal step in the maturation of the large subunit of [NiFe]-hydrogenases. They remove a C-terminal extension from the precursor of the subunit, triggering a conformational switch that results in the bridging of the Fe and Ni atoms of the metal centre via the thiolate of a cysteine residue and in closure of the centre. This review summarizes what is known about the structure of the protein, its substrate specificity and its possible reaction mechanism.

scholarly journals X-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2

2020 ◽  
Vol 477 (19) ◽  
pp. 3819-3832
Author(s):  
Emilia M. Marijanovic ◽  
Karolina Weronika Swiderska ◽  
James Andersen ◽  
Jasmin C. Aschenbrenner ◽  
Chaille T. Webb ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Toxoplasma Gondii ◽  
Drug Target ◽  
Structure And Function ◽  
Parasitic Disease ◽  
Vaccine Candidates ◽  
X Ray ◽  
Structure Activity ◽  
Comparative Structure ◽  
And Function

Toxoplasmosis is a parasitic disease caused by infection with Toxoplasma gondii that currently has few therapeutic options. The M1 aminopeptidase enzymes have been shown to be attractive targets for anti-parasitic agents and/or vaccine candidates, suggesting potential to re-purpose inhibitors between parasite M1 aminopeptidase targets. The M1 aminopeptidase TgAPN2 has been suggested to be a potential new drug target for toxoplasmosis. Here we investigate the structure and function of TgAPN2, a homologue of the antimalarial drug target PfA-M1, and evaluate the capacity to use inhibitors that target PfA-M1 against TgAPN2. The results show that despite a similar overall fold, the TgAPN2 has a unique substrate specificity and inhibition profile. Sequence and structure differences are investigated and show how comparative structure-activity relationships may provide a route to obtaining potent inhibitors of TgAPN2.

scholarly journals The role of cysteines in the structure and function of OGG1

2020 ◽  
pp. jbc.RA120.016126
Author(s):  
Katarina Wang ◽  
Marah Maayah ◽  
Joann B. Sweasy ◽  
Khadijeh S. Alnajjar
Keyword(s):  
Oxidative Stress ◽  
Excision Repair ◽  
Cysteine Residue ◽  
Structure And Function ◽  
Cysteine Residues ◽  
Lyase Activity ◽  
Integral Role ◽  
Base Excision ◽  
And Function

8-oxoguanine glycosylase (OGG1) is a base excision repair enzyme responsible for the recognition and removal of 8-oxoguanine, a commonly occurring oxidized DNA modification. OGG1 prevents the accumulation of mutations and regulates the transcription of various oxidative stress-response genes. In addition to targeting DNA, oxidative stress can affect proteins like OGG1 itself, specifically at cysteine residues. Previous work has shown that the function of OGG1 is sensitive to oxidants, with the cysteine residues of OGG1 being the most likely site of oxidation. Due to the integral role of OGG1 in maintaining cellular homeostasis under oxidative stress, it is important to understand the effect of oxidants on OGG1 and the role of cysteines in its structure and function. In this study, we investigate the role of the cysteine residues in the function of OGG1 by mutating and characterizing each cysteine residue. Our results indicate that the cysteines in OGG1 fall into four functional categories: those that are necessary for (1) glycosylase activity (C146 and C255), (2) lyase activity (C140S, C163, C241 and C253), (3) structural stability (C253), and (4) those with no known function (C28 and C75). These results suggest that under conditions of oxidative stress, cysteine can be targeted for modifications, thus altering the response of OGG1 and affecting its downstream cellular functions.

Structure and function of neural networks in the retina

1988 ◽  
Vol 46 ◽  
pp. 26-27
Author(s):  
Peter Sterling
Keyword(s):  
Ganglion Cells ◽  
Three Dimensional ◽  
Structure And Function ◽  
Synaptic Connections ◽  
Visual Axis ◽  
One Dimensional ◽  
Cat Retina ◽  
Ultrathin Sections ◽  
And Function ◽  
Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

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