Identification of Function and Mechanistic Insights of Guanine Deaminase fromNitrosomonas europaea: Role of the C-Terminal Loop in Catalysis

Biochemistry ◽  
2013 ◽  
Vol 52 (20) ◽  
pp. 3512-3522 ◽  
Author(s):  
Aruna Bitra ◽  
Bhukya Hussain ◽  
Ajay Singh Tanwar ◽  
Ruchi Anand
Keyword(s):  
Guanine Deaminase ◽  
Terminal Loop

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.

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.

Role of the 14-3-3 C-terminal loop in ligand interaction

2002 ◽  
Vol 49 (3) ◽  
pp. 321-325 ◽  
Author(s):  
Amy B. Truong ◽  
Shane C. Masters ◽  
Hongzhu Yang ◽  
Haian Fu
Keyword(s):  
Ligand Interaction ◽  
Terminal Loop

scholarly journals Role of Asn2 and Glu7 residues in the oxidative folding and on the conformation of theN-terminal loop of apamin

Biopolymers ◽  
2007 ◽  
Vol 86 (5-6) ◽  
pp. 447-462 ◽  
Author(s):  
Dung Le-Nguyen ◽  
Laurent Chiche ◽  
François Hoh ◽  
Marie France Martin-Eauclaire ◽  
Christian Dumas ◽  
...  
Keyword(s):  
Oxidative Folding ◽  
Terminal Loop

scholarly journals A Lys49 PhospholipaseA2, Isolated fromBothrops asperSnake Venom, Induces Lipid Droplet Formation in Macrophages Which Depends on Distinct Signaling Pathways and the C-Terminal Region

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Karina Cristina Giannotti ◽  
Elbio Leiguez ◽  
Vanessa Moreira ◽  
Neide Galvão Nascimento ◽  
Bruno Lomonte ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Protein Kinases ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Terminal Sequence ◽  
Pharmacological Interventions ◽  
C Terminus ◽  
Inflammatory Mechanism ◽  
Terminal Loop

MT-II, a Lys49PLA2homologue devoid of catalytic activity fromB. aspervenom, stimulates inflammatory events in macrophages. We investigated the ability of MT-II to induce formation of lipid droplets (LDs), key elements of inflammatory responses, in isolated macrophages and participation of protein kinases and intracellular PLA2s in this effect. Influence of MT-II on PLIN2 recruitment and expression was assessed, and the effects of some synthetic peptides on LD formation were further evaluated. At noncytotoxic concentrations, MT-II directly activated macrophages to form LDs. This effect was reproduced by a synthetic peptide corresponding to the C-terminal sequence 115–129 of MT-II, evidencing the critical role of C-terminus for MT-II-induced effect. Moreover, MT-II induced expression and recruitment of PLIN2. Pharmacological interventions with specific inhibitors showed that PKC, PI3K, ERK1/2, and iPLA2, but notP38MAPKor cPLA2, signaling pathways are involved in LD formation induced by MT-II. This sPLA2homologue also induced synthesis of PGE2that colocalized to LDs. In conclusion, MT-II is able to induce formation of LDs committed to PGE2formation in a process dependent on C-terminal loop engagement and regulated by distinct protein kinases and iPLA2. LDs may constitute an important inflammatory mechanism triggered by MT-II in macrophages.

Role of an N-Terminal Loop in the Secondary Structural Change of Photoactive Yellow Protein†

Biochemistry ◽  
2003 ◽  
Vol 42 (47) ◽  
pp. 13893-13900 ◽  
Author(s):  
Miki Harigai ◽  
Yasushi Imamoto ◽  
Hironari Kamikubo ◽  
Yoichi Yamazaki ◽  
Mikio Kataoka
Keyword(s):  
Structural Change ◽  
Photoactive Yellow Protein ◽  
Terminal Loop ◽  
Secondary Structural Change

scholarly journals The role of the N-terminal loop in the function of the colicin E7 nuclease domain

2013 ◽  
Vol 18 (3) ◽  
pp. 309-321 ◽  
Author(s):  
Anikó Czene ◽  
Eszter Németh ◽  
István G. Zóka ◽  
Noémi I. Jakab-Simon ◽  
Tamás Körtvélyesi ◽  
...  
Keyword(s):  
Nuclease Domain ◽  
Colicin E7 ◽  
Terminal Loop
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