scholarly journals A drought‐responsive rice amidohydrolase is the elusive plant guanine deaminase with the potential to modulate the epigenome

2021 ◽  
Author(s):  
Dhananjay Gotarkar ◽  
Toshisangba Longkumer ◽  
Naoki Yamamoto ◽  
Amrit Kaur Nanda ◽  
Tamara Iglesias ◽  
...  
Keyword(s):  
Guanine Deaminase

scholarly journals Crystal Structure of Bacillus subtilis Guanine Deaminase

2004 ◽  
Vol 279 (34) ◽  
pp. 35479-35485 ◽  
Author(s):  
Shwu-Huey Liaw ◽  
Yu-Jui Chang ◽  
Cheng-Tsung Lai ◽  
Hui-Chuan Chang ◽  
Gu-Gang Chang
Keyword(s):  
Crystal Structure ◽  
Bacillus Subtilis ◽  
Guanine Deaminase

Insights into the Dual Shuttle Catalytic Mechanism of Guanine Deaminase

2021 ◽  
Author(s):  
Asmita Sen ◽  
Vandana Gaded ◽  
Prabha Jayapal ◽  
Gopalan Rajaraman ◽  
Ruchi Anand
Keyword(s):  
Catalytic Mechanism ◽  
Guanine Deaminase

scholarly journals Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

2021 ◽  
Vol 22 (22) ◽  
pp. 12501
Author(s):  
Kyung Ah Cheong ◽  
In Sup Kil ◽  
Hyuk Wan Ko ◽  
Ai-Young Lee
Keyword(s):  
Uric Acid ◽  
The Elderly ◽  
Epidermal Keratinocytes ◽  
Seborrheic Keratosis ◽  
Human Epidermal Keratinocytes ◽  
Skin Hyperpigmentation ◽  
Guanine Deaminase ◽  
Acid Release ◽  
Skin Specimen

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (GDA) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA-overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging.

Guanine deaminase

1991 ◽  
pp. 993-997
Author(s):  
Dietmar Schomburg ◽  
Margit Salzmann
Keyword(s):  
Guanine Deaminase

scholarly journals Structure based protein engineering to confer selectivity of guanine deaminase

2014 ◽  
Vol 70 (a1) ◽  
pp. C437-C437
Author(s):  
Aruna Bitra ◽  
Ruchi Anand
Keyword(s):  
Crystal Structures ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Catalytic Efficiency ◽  
Structural Basis ◽  
Active Site Residues ◽  
X Ray ◽  
Secondary Activity ◽  
Guanine Deaminase ◽  
Differential Selectivity

Guanine deaminases (GDs) are important enzymes involved in both purine metabolism and nucleotide anabolism pathways. Here we present the molecular and catalytic mechanism of NE0047 and use the information obtained to engineer specific enzyme activities. NE0047 from Nitrosomonas europaea was found to be a high fidelity guanine deaminase (catalytic efficiency of 1.2 × 105 M–1 s–1). However; it exhibited secondary activity towards the structurally non-analogous triazine based compound ammeline. The X-ray structure of NE0047 in the presence of the substrate analogue 8-azaguanine help establish that the enzyme exists as a biological dimer and both the proper closure of the C-terminal loop and cross talk via the dimeric interface is crucial for conferring catalytic activity. It was further ascertained that the highly conserved active site residues Glu79 and Glu143 facilitate the deamination reaction by serving as proton shuttles. Moreover, to understand the structural basis of dual substrate specificity, X-ray structures of NE0047 in complex with a series of nucleobase analogs, nucleosides and substrate ammeline were determined. The crystal structures demonstrated that any substitutions in the parent substrates results in the rearrangement of the ligand in a catalytically unfavorable orientation and also impede the closure of catalytically important loop, thereby abrogating activity. However, ammeline was able to adopt a catalytically favorable orientation which, also allowed for proper loop closure. Based on the above knowledge of the crystal structures and the catalytic mechanism, the active site was subsequently engineered to fine-tune NE0047 activity. The mutated versions of the enzyme were designed so that they can function either exclusively as a GD or serve as specific ammeline deaminases. For example, mutations in the active site E143D and N66A confer the enzyme to be an unambiguous GD with no secondary activity towards ammeline. On the other hand, the N66Q mutant of NE0047 only deaminates ammeline. Additionally, a series of crystal structures of the mutant versions were solved that shed light on the structural basis of this differential selectivity.

scholarly journals Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2637
Author(s):  
Joon Min Jung ◽  
Tai Kyung Noh ◽  
Soo Youn Jo ◽  
Su Yeon Kim ◽  
Youngsup Song ◽  
...  
Keyword(s):  
Stem Cell Factor ◽  
Small Interfering Rna ◽  
Skin Pigmentation ◽  
Epidermal Keratinocytes ◽  
Melanin Content ◽  
Human Epidermal Keratinocytes ◽  
Guanine Deaminase ◽  
Keratinocyte Culture ◽  
Interfering Rna

Epidermal keratinocytes are considered as the most important neighboring cells that modify melanogenesis. Our previous study used microarray to show that guanine deaminase (GDA) gene expression is highly increased in melasma lesions. Hence, we investigated the role of GDA in skin pigmentation. We examined GDA expression in post-inflammatory hyperpigmentation (PIH) lesions, diagnosed as Riehl’s melanosis. We further investigated the possible role of keratinocyte-derived GDA in melanogenesis by quantitative PCR, immunofluorescence staining, small interfering RNA-based GDA knockdown, and adenovirus-mediated GDA overexpression. We found higher GDA positivity in the hyperpigmentary lesional epidermis than in the perilesional epidermis. Both UVB irradiation and stem cell factor (SCF) plus endothelin-1 (ET-1) were used, which are well-known melanogenic stimuli upregulating GDA expression in both keratinocyte culture alone and keratinocyte and melanocyte coculture. GDA knockdown downregulated melanin content, while GDA overexpression promoted melanogenesis in the coculture. When melanocytes were treated with UVB-exposed keratinocyte-conditioned media, the melanin content was increased. Also, GDA knockdown lowered SCF and ET-1 expression levels in keratinocytes. GDA in epidermal keratinocytes may promote melanogenesis by upregulating SCF and ET-1, suggesting its role in skin hyperpigmentary disorders.

Kinetic measurement of guanine deaminase in serum with a centrifugal analyzer.

1981 ◽  
Vol 27 (4) ◽  
pp. 560-561 ◽  
Author(s):  
Y Nishikawa ◽  
K Fukumoto
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Kinetic Method ◽  
Reference Interval ◽  
Healthy Humans ◽  
Automated Method ◽  
Enzyme Substrate ◽  
Guanine Deaminase ◽  
One Step ◽  
Lag Period ◽  
Method R

Abstract We describe an enzymic, one-step kinetic method for determination of guanine deaminase (guanase, EC 3.5.4.3) in serum with a centrifugal analyzer. A combined enzyme-substrate system consists of the enzymes xanthine oxidase, catalase, and aldehyde dehydrogenase, the coenzyme NAD+, the substrate guanine, and ethanol in tris(hydroxymethyl)methylamine buffer, with KCl added as activator for aldehyde dehydrogenase. The method requires only 40 microL of sample. Guanase activity in 28 samples can be determined within 10 min by setting a 4-min lag period. The increase in absorbance at 340 nm is linearly proportional to the activity of guanase to 60 U/L. Within-run precision (CV) was 1.32 to 4.50% over the range studied. Day-to-day precision corresponds to CVs of 4.8 to 7.2% over the same range of guanase activity. The reference interval, as calculated from data on 25 healthy humans, was 0 to 1.02 U/L. The enzymic automated method shows good correlation with Caraway's (Clin. Chem. 12: 187, 1966) method (r = 0.949).

ChemInform Abstract: NEW IMIDAZOLYLTHIOCARBAMIDES AS GUANINE DEAMINASE INHIBITORS

1980 ◽  
Vol 11 (22) ◽  
Author(s):  
A. K. SAXENA ◽  
S. AHMAD ◽  
K. SHANKER ◽  
K. P. BHARGAVA ◽  
K. KISHOR
Keyword(s):  
Guanine Deaminase
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