Article
Genetics & Heredity
Jian Jiao, Yan Xia, Yingli Zhang, Xueli Wu, Chonghuai Liu, Jiancan Feng, Xianbo Zheng, Shangwei Song, Tuanhui Bai, Chunhui Song, Miaomiao Wang, Hongguang Pang
Summary: This study revealed a possible role for bacterial phenylalanine 4-hydroxylase (PAH) in controlling 5-HTP and melatonin biosynthesis in bacteria. Deletion of PAH in Pseudomonas fluorescens resulted in a decline in 5-HTP levels and decreased resistance to abiotic stress. The findings expanded the current knowledge of melatonin production in microorganisms.
FRONTIERS IN GENETICS
(2021)
Review
Microbiology
Sara Goncalves, Daniela Nunes-Costa, Sandra Morais Cardoso, Nuno Empadinhas, John David Marugg
Summary: Serotonin is a vital compound found in animals, plants, and bacteria. It plays critical roles in regulating body functions and its depletion is associated with neurological disorders in humans. Investigating the biosynthetic pathways of serotonin in bacteria, which may serve as a potential source of serotonin, could lead to important discoveries and the development of new therapeutic strategies.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katsuya Miyajima, Yusuke Sudo, Sho Sanechika, Yoshitaka Hara, Mieko Horiguchi, Feng Xu, Minori Suzuki, Satoshi Hara, Koichi Tanda, Ken-ichi Inoue, Masahiko Takada, Nozomu Yoshioka, Hirohide Takebayashi, Masayo Mori-Kojima, Masahiro Sugimoto, Chiho Sumi-Ichinose, Kazunao Kondo, Keizo Takao, Tsuyoshi Miyakawa, Hiroshi Ichinose
Summary: Increasing evidence suggests that peripheral amino acid metabolism is involved in the pathophysiology of neuropsychiatric disorders, but the molecular mechanisms are largely unknown. This study found that disturbances in tetrahydrobiopterin (BH4) metabolism can lead to hyperphenylalaninemia and monoamine deficiency in the brain, potentially contributing to the development of anxiety-related psychiatric disorders.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Yeri Choi, Sang-Woo Han, Jun-Sung Kim, Youngho Jang, Jong-Shik Shin
Summary: The study demonstrates that AADC-BA from Bacillus atrophaeus has a broad substrate specificity, allowing for efficient synthesis of various aromatic biogenic amines, including neurotransmitters. Experimental results show that AADC-BA can be used for the production of serotonin and other substances.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Nutrition & Dietetics
Fatma Ilgaz, Cyril Marsaux, Alex Pinto, Rani Singh, Carmen Rohde, Erdem Karabulut, Hulya Gokmen-Ozel, Mirjam Kuhn, Anita MacDonald
Summary: For PKU patients undergoing BH4 treatment, some can discontinue protein substitute usage while others still require it. Despite maintaining normal growth, micronutrient deficiencies are observed in patients on BH4 therapy.
Article
Genetics & Heredity
Kazuki Takabatake, Kazuki Izawa, Motohiro Akikawa, Keisuke Yanagisawa, Masahito Ohue, Yutaka Akiyama
Summary: Metagenomic analysis requires high-precision homology searches on large amounts of sequencing data, but commonly used software like NCBI BLAST lacks the speed needed for current DNA sequencers. This paper introduces a new, high-performance homology search algorithm that is faster than existing tools for <= 120,000 queries.
Article
Chemistry, Medicinal
Nibal Betari, Knut Teigen, Kristoffer Sahlholm, Jan Haavik
Summary: The study found that beclomethasone dipropionate can act as a stabilizer of TPHs, with pharmacological effects, and may inspire further development of steroid scaffolds as potential antidepressant drugs.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Maria Teresa Bueno-Carrasco, Jorge Cuellar, Marte I. Flydal, Cesar Santiago, Trond-Andre Krakenes, Rune Kleppe, Jose R. Lopez-Blanco, Miguel Marcilla, Knut Teigen, Sara Alvira, Pablo Chacon, Aurora Martinez, Jose M. Valpuesta
Summary: Tyrosine hydroxylase (TH) is a key enzyme in the synthesis of dopamine (DA) and other catecholamines. This study used Cryo-EM to determine the structures of human TH with and without DA, as well as S40 phosphorylated TH. The study revealed the inhibitory and stabilizing effects of DA, as well as the counteraction by S40 phosphorylation, providing insights into the regulatory mechanisms of TH and dopamine homeostasis.
NATURE COMMUNICATIONS
(2022)
Review
Biotechnology & Applied Microbiology
Yingying Wang, Yan Chen, Alei Zhang, Kequan Chen, Pingkai Ouyang
Summary: Serotonin, a monoamine neurotransmitter, plays a crucial role in the modulation of the nervous system. Impairments in its synthesis and homeostasis are linked to various disorders, including depression, Parkinson's disease, and anxiety. Current methods of obtaining serotonin are time-consuming, low yield, and rely on unstable raw material supply. However, with the advancements in synthetic biology, microbial synthesis of serotonin has gained attention for its advantages in terms of production cycle, continuity, and environmental friendliness. Despite this, the yield of serotonin is still insufficient for industrialization, prompting the need for strategies to increase its production.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Microbiology
Kai Chen, Xihui Xu, Muji Yang, Tairong Liu, Bin Liu, Jianchun Zhu, Baozhan Wang, Jiandong Jiang
Summary: This study reveals the selective advantages of genetic redundancy in overcoming metabolic disturbance caused by structural analogues. In Pigmentiphaga sp. strain H8, the genes phbh1 and phbh2 are responsible for processing the anthropogenic pollutant 3-Br-4-HB, while phbh3 processes the natural intermediate 4-HB. The presence of phbh1 and phbh2 not only enables the utilization of 3-Br-4-HB but also ensures the safety of 4-HB catabolism.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Oncology
Kavita Sharma, Aastha Mishra, Himanshu Singh, Tashi Thinlas, M. A. Qadar Pasha
Summary: This study found that the DNA methylation levels in the oxygen-sensing genes EGLN1 and HIF1AN were altered in individuals with high-altitude pulmonary edema (HAPE). Specific CpG sites in EGLN1 showed significant associations with the risk of HAPE. The methylation levels in EGLN1 correlated with plasma levels of PHD2 and peripheral blood oxygen saturation. These findings suggest a functional epigenetic relevance of EGLN1 in HAPE pathophysiology.
CLINICAL EPIGENETICS
(2022)
Article
Endocrinology & Metabolism
Somdattaa Ray, Hansashree Padmanabha, Vykuntaraju K. Gowda, Rohan Mahale, Rita Christopher, Shruthy Sreedharan, Debjyoti Dhar, Mahesh Kamate, Madhu Nagappa, Maya Bhat, Rammurthy Anjanappa, Gautham Arunachal, M. Pooja, P. S. Mathuranath, S. R. Chandra
Summary: Disorders of tetrahydrobiopterin metabolism are rare inherited neurotransmitter disorders that primarily manifest in infancy or childhood with developmental delay, neuroregression, epilepsy, movement disorders, and autonomic symptoms. This retrospective study in South India identified nine genetically confirmed cases of tetrahydrobiopterin metabolism disorders. The study found that early treatment with dietary restrictions and medication can improve the outcomes of patients with tetrahydrobiopterin deficiencies.
METABOLIC BRAIN DISEASE
(2022)
Article
Chemistry, Physical
Heng Zhang, Yuanxin Cheng, Qiongqiong Ge, Jinhai Yu, Guangcheng Fu, Yunfan Gao, Yu Wang, Yunhui Ye, Jianquan Du, Qingcai Jiao, Junzhong Liu
Summary: This article investigates the dynamic behavior of aromatic L-amino acid decarboxylase (BaAADC) from Bacillus atrophaeus at different temperatures and explores the relationship between its thermal stability and internal residues. The study reveals that high temperatures alter the structure of BaAADC, particularly at the active site, leading to changes in hydrogen bonding and amino acid flexibility. Key residues and salt bridges are identified, which partially contribute to the inactivation of BaAADC at high temperatures. Strategies for improving the thermostability of BaAADC are also discussed.
COMPUTATIONAL AND THEORETICAL CHEMISTRY
(2023)
Review
Health Care Sciences & Services
Sudipt Kumar Dalei, Nidhi Adlakha
Summary: This article discusses the characteristics and treatment methods of the inherited genetic disorder phenylketonuria, emphasizing the importance of in-depth evaluation of medicated diet expenses and possible solutions.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2022)
Article
Chemistry, Medicinal
Afrah Khairallah, Caroline J. Ross, Ozlem Tastan Bishop
Summary: Guanosine triphosphate (GTP) cyclohydrolase I (GCH1) is a crucial enzyme involved in the biosynthesis of folate and tetrahydrobiopterin, essential for DNA replication, cell division, and neurotransmitter production. Understanding the intrinsic dynamics and allosteric modulation of GCH1 structure has potential implications for developing new antineuropathic treatments and antimalarial drugs. The study identified key sites regulating the GCH1 enzyme activity and proposed a starting point for drug development targeting neuropathic disorders and malaria.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Marte I. Flydal, Trond-Andre Krakenes, Mary Dayne S. Tai, Maria P. A. Tran, Knut Teigen, Aurora Martinez
Summary: Tyrosine hydroxylase plays a critical role in dopamine synthesis and deficiencies in TH can lead to THD. Screening a drug library revealed levalbuterol as a potential stabilizer of TH, reducing the enzyme's sensitivity to dopamine and potentially aiding in the treatment of TH-related disorders.
Article
Biochemistry & Molecular Biology
Maria S. Eriksen, Oleksii Nikolaienko, Erik I. Hallin, Sverre Grodem, Helene J. Bustad, Marte I. Flydal, Ian Merski, Tomohisa Hosokawa, Daniela Lascu, Shreeram Akerkar, Jorge Cuellar, James J. Chambers, Rory O'Connell, Gopinath Muruganandam, Remy Loris, Christine Touma, Tambudzai Kanhema, Yasunori Hayashi, Margaret M. Stratton, Jose M. Valpuesta, Petri Kursula, Aurora Martinez, Clive R. Bramham
Summary: The study identified a 28-amino-acid stretch in the mammalian Arc N-terminal domain that is crucial for self-association and a 7-residue oligomerization motif critical for virus-like capsid formation. The atomic-resolution crystal structure of the oligomerization region peptide revealed an antiparallel coiled-coil interface supporting NT-NT domain interactions in Arc oligomerization. The study also showed that Arc mRNA enhances higher-order oligomerization dependent on the oligomerization motif, leading to the formation of virus-like capsids.
Review
Biochemistry & Molecular Biology
Helene J. Bustad, Juha P. Kallio, Marta Vorland, Valeria Fiorentino, Sverre Sandberg, Caroline Schmitt, Aasne K. Aarsand, Aurora Martinez
Summary: Acute intermittent porphyria (AIP) is a rare autosomal dominant inherited disease caused by mutations in the HMBS gene, leading to acute attacks and long-term complications. Treatment options are limited, but there are emerging therapeutic approaches with potential prophylactic correction of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Maria T. Bezem, Fredrik G. Johannessen, Trond-Andre Krakenes, Michael J. Sailor, Aurora Martinez
Summary: The study investigates the interaction between TH and pSiNPs, showing that TH can bind with pSiNPs at pH 7, but aggregates at pH 6. However, the activity of TH is unlikely affected by the binding to pSiNPs.
MOLECULAR PHARMACEUTICS
(2021)
Article
Multidisciplinary Sciences
Helene J. Bustad, Juha P. Kallio, Mikko Laitaoja, Karen Toska, Inari Kursula, Aurora Martinez, Janne Janis
Summary: Research showed structural differences between AIP-associated mutants and wild-type PBGD, and highlighted the significant role of Arg173 in the polypyrrole elongation mechanism.
Article
Multidisciplinary Sciences
Oscar Aubi, Karina S. Prestegard, Kunwar Jung-KC, Tie-Jun Sten Shi, Ming Ying, Ann Kari Grindheim, Tanja Scherer, Arve Ulvik, Adrian McCann, Endy Spriet, Beat Thony, Aurora Martinez
Summary: Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH) and can lead to neurotoxicity. Here the authors describe a mouse model of PKU based on a mutation in phenylalanine hydroxylase (R261Q) which replicates traits of this disease and shows a proteostasis defect and oxidative stress, implying a gain-of-function contribution to the disease phenotype.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Kai Waloen, Kunwar Jung-KC, Elisa D. Vecchia, Sunil Pandey, Norbert Gasparik, Anne Doskeland, Sudarshan Patil, Rune Kleppe, Jozef Hritz, William H. J. Norton, Aurora Martinez, Jan Haavik
Summary: Ebselen has been identified as a covalent ligand that destabilizes 14-3-3 proteins, particularly affecting the binding of 14-3-3 with its partner proteins. This destabilization leads to decreased levels of 14-3-3 and altered protein interaction networks, showing promise for therapeutic applications in cancer and neuropsychiatric disorders.
MOLECULAR PHARMACOLOGY
(2021)
Article
Oncology
Leire Dublang, Jarl Underhaug, Marte Flydal, Lorea Velasco-Carneros, Jean-Didier Marechal, Fernando Moro, Maria Dolores Boyano, Aurora Martinez, Arturo Muga
Summary: High levels of Heat shock proteins (Hsps) are often associated with poor prognosis, tumor progression, and resistance to treatment in specific cancers. This study demonstrates the potential of using the small chemical compound pinaverium bromide, originally used for gastrointestinal disorders, as an antitumor drug by targeting Hsp70 and Hsp110 families. The compound inhibits the substrate remodeling ability of the Hsp70 system, specifically targeting melanoma cells, and shows promise as a novel therapeutic approach for cancer treatment.
Article
Biochemistry & Molecular Biology
Pau Martin-Malpartida, Emil Hausvik, Jarl Underhaug, Carles Torner, Aurora Martinez, Maria J. Macias
Summary: To simplify the analysis steps in target-based biophysical assays, we developed the HTSDSF explorer, a versatile, all-in-one, user-friendly application suite. It helps users quickly analyze and select primary hits, and determines preliminary binding constants through dose-response assays.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria Teresa Bueno-Carrasco, Jorge Cuellar, Marte I. Flydal, Cesar Santiago, Trond-Andre Krakenes, Rune Kleppe, Jose R. Lopez-Blanco, Miguel Marcilla, Knut Teigen, Sara Alvira, Pablo Chacon, Aurora Martinez, Jose M. Valpuesta
Summary: Tyrosine hydroxylase (TH) is a key enzyme in the synthesis of dopamine (DA) and other catecholamines. This study used Cryo-EM to determine the structures of human TH with and without DA, as well as S40 phosphorylated TH. The study revealed the inhibitory and stabilizing effects of DA, as well as the counteraction by S40 phosphorylation, providing insights into the regulatory mechanisms of TH and dopamine homeostasis.
NATURE COMMUNICATIONS
(2022)
Review
Health Care Sciences & Services
Gyrid Nygaard, Peter D. Szigetvari, Ann Kari Grindheim, Peter Ruoff, Aurora Martinez, Jan Haavik, Rune Kleppe, Marte Flydal
Summary: Dopa-responsive dystonia (DRD) is a rare movement disorder linked to defective dopamine synthesis, mainly associated with mutations in the GCH1 gene. However, some patients do not respond well to L-DOPA treatment, especially in severe cases of TH deficiency. This highlights the need for more effective and personalized treatment options.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Multidisciplinary Sciences
Sigurbjorn Markusson, Erik Hallin, Helene J. Bustad, Arne Raasakka, Ju Xu, Gopinath Muruganandam, Remy Loris, Aurora Martinez, Clive R. Bramham, Petri Kursula
Summary: Activity-regulated cytoskeleton-associated protein (Arc) plays a vital role in synaptic plasticity and memory formation. This study used high-affinity anti-Arc nanobodies to investigate the structure and function of Arc. The results suggest that the N-terminal domain of Arc is involved in membrane binding, while the C-terminal domain binds to postsynaptic protein ligands. Furthermore, the NTD and CTD are important for Arc oligomerisation and assembly of capsids.
Letter
Oncology
Georgios Makris, Semih Kayhan, Marvin Kreuzer, Veronique Rufenacht, Erica Faccin, Jarl Underhaug, Carmen Diez-Fernandez, Philip A. Knobel, Martin Poms, Nadine Gougeard, Vicente Rubio, Aurora Martinez, Martin Pruschy, Johannes Haberle
CANCER COMMUNICATIONS
(2023)
Article
Biology
Svein Isungset Stove, Age Aleksander Skjevik, Knut Teigen, Aurora Martinez
Summary: This study identifies several approved drugs as inhibitors of rat VMAT2 and suggests their potential implications for drug repurposing and therapy development.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Helene J. Bustad, Marthe S. Christie, Mikko Laitaoja, Aasne K. Aarsand, Aurora Martinez, Janne Janis, Juha P. Kallio
Summary: The HMBS enzyme plays a crucial role in haem biosynthesis through the coupling of porphobilinogens. Mutations in the enzyme can affect catalytic function and product release.