Article
Polymer Science
Neil L. Forsythe, Mikayla F. Tan, Daniele Vinciguerra, Jacquelin Woodford, Adam Z. Stieg, Heather D. Maynard
Summary: In this study, a new method for the preparation of noncovalent enzyme nanogels (ENGs) was developed, utilizing a heterobifunctional, photocleavable monomer. The stability of the enzyme in the noncovalent nanogels was found to be higher compared to the enzyme alone, indicating the potential usefulness of this method for enzyme stabilization.
Article
Pharmacology & Pharmacy
Lyubov Dyshlyuk, Stanislav Sukhikh, Svetlana Noskova, Svetlana Ivanova, Alexander Prosekov, Olga Babich
Summary: The study found that l-phenylalanine ammonia-lyase successfully penetrates the monolayer of liver cells after release from capsules, with no significant impact of the capsule shell on absorption. The encapsulated form of PAL shows high efficiency in correcting phenylketonuria, as confirmed by in vitro experiments.
Article
Biochemistry & Molecular Biology
Kunal Meena, Shahenvaz Alam, Sudipt Kumar Dalei, Sunil Kumar Khare, Nidhi Adlakha
Summary: A sustainable method using immobilized phenylalanine ammonia lyase (PAL) is described for generating a low-phenylalanine protein supplement for phenylketonuria patients. The PAL enzyme deaminates phenylalanine to trans-cinnamic acid. The method involves optimizing high cell density cultivation and immobilizing the AvPAL protein on multiwall carbon nanotubes.
PROCESS BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Tolga Sari, Sureyya Dede, Busra Yusufoglu, Emine Karakus
Summary: A new fluorometric method based on PAL and OPA has been developed for the determination of L-phenylalanine in serum samples, which is practical, easy to operate, low cost, highly sensitive, and selective, and can also be used for the simultaneous determination of ammonia in human serum samples.
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
(2022)
Article
Biology
Yu Jiang, Bingbing Sun, Fenghui Qian, Feng Dong, Chongmao Xu, Wuling Zhong, Rui Huang, Qiwei Zhai, Yu Jiang, Sheng Yang
Summary: Phenylketonuria is a disease that affects the degradation of phenylalanine, but engineered probiotics have shown promise in degrading phenylalanine and treating the disease. However, the limited transmembrane transport of phenylalanine hinders the effectiveness of the probiotics. This study successfully overcame the transportation problem in E. coli and reduced the phenylalanine concentration in a mouse model, demonstrating the potential for PKU therapy.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Endocrinology & Metabolism
Mika Ishige, Tetsuya Ito, Takashi Hamazaki, Mitsuhiro Kuwahara, Lawrence Lee, Haruo Shintaku
Summary: This study provides evidence supporting the use of pegvaliase in Japanese adults with PKU, demonstrating its ability to reduce blood phenylalanine levels effectively and with manageable safety.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Rakhshan Ahmad, Neha Sami, Gulnar Perveen, Tasneem Fatma
Summary: Phenylalanine ammonia lyase (PAL) plays a crucial role in the formation of secondary metabolites and has various clinical and commercial applications. PAL has high substrate specificity and catalytic efficacy, making it valuable in metabolic engineering, enzyme replacement therapy, and other fields.
Review
Genetics & Heredity
April D. Adams, Moises O. Fiesco-Roa, Lawrence Wong, Gabrielle P. Jenkins, Jennifer Malinowski, Olivia M. Demarest, Paul G. Rothberg, ACMG Therapeutics Comm
Summary: The study aimed to evaluate the optimal serum phenylalanine (Phe) levels for patients with phenylalanine hydroxylase (PAH) deficiency and found that lowering Phe to <= 360 mu mol/L was highly effective in improving outcomes, although medication treatment may cause adverse events.
GENETICS IN MEDICINE
(2023)
Article
Neurosciences
Angela T. S. Wyse, Tiago M. dos Santos, Bianca Seminotti, Guilhian Leipnitz
Summary: Phenylketonuria is a metabolic disorder caused by phenylalanine hydroxylase deficiency, leading to neurological dysfunction and hepatic damage in severe cases. Studies have shown that phenylalanine and its metabolites may induce toxicity by affecting mitochondrial bioenergetics and oxidative status.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemical Research Methods
Vikas D. Trivedi, Karishma Mohan, Todd C. Chappell, Zachary J. S. Mays, Nikhil U. Nair
Summary: Transcription factor (TF)-based biosensors are ideal reagents for high-throughput enzyme and strain engineering, but they often face issues with crosstalk. By desensitizing the biosensor and coupling with orthogonal prescreen, the enrichment of cheater cells can be successfully reduced.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Jieun Kim, Seungbok Lee, Jaemeun Lee, Jong-Chan Park, Kyung Hyun Kim, Jung Min Ko, Sun-Hyun Park, Seung-Ki Kim, Inhee Mook-Jung, Ji Yeoun Lee
Summary: Phenylketonuria (PKU) is a genetic metabolic disorder that leads to the accumulation of phenylalanine in the blood. This study utilized human induced pluripotent stem cell (iPSC)-derived cerebral organoids to investigate the neurotoxicity of hyperphenylalaninemia. The findings suggest that phenylalanine exposure may contribute to microcephaly and abnormal cortical expansion in the developing human brain.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Chemistry, Physical
Gabor Koplanyi, Evelin Santa-Bell, Zsofia Molnar, Gergo Daniel Toth, Muriel Jozo, Andras Szilagyi, Ferenc Ender, Bela Pukanszky, Beata G. Vertessy, Laszlo Poppe, Diana Balogh-Weiser
Summary: This study presents a successful immobilization of plant-derived PcPAL enzyme in PLA nanofibers using emulsion electrospinning for the ammonia elimination reaction from l-phenylalanine.
Article
Genetics & Heredity
Deborah A. Bilder, Georgianne L. Arnold, David Dimmock, Mitzie L. Grant, Darren Janzen, Nicola Longo, Mina Nguyen-Driver, Elaina Jurecki, Markus Merilainen, Gianni Amato, Susan Waisbren
Summary: The study shows that there is a relationship between phenylalanine levels and inattention in adult PKU patients, suggesting that reducing phenylalanine levels may improve symptoms of inattention. The greatest improvements in inattention symptoms were seen in participants with the largest reductions in plasma phenylalanine levels, supporting the value of this as a therapeutic goal.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Biochemistry & Molecular Biology
Yu Qin, Qiue Li, Qiuju An, Dexin Li, Sipei Huang, Yongyang Zhao, Weijia Chen, Jiayu Zhou, Hai Liao
Summary: Drought is a key threat to plants and agriculture, and the role of the enzyme phenylalanine ammonia lyase (PAL) in drought tolerance has been explored in this study. A PAL member called FuPAL1 was isolated from the alpine pharmaceutical plant Fritillaria unibracteata. FuPAL1 was found to play a role in the ammonization process and was involved in substrate binding and catalysis. Transgenic Arabidopsis plants with FuPAL1 showed increased levels of lignin and salicylic acid and enhanced drought tolerance. These findings suggest that FuPAL1 could be a valuable target for improving drought resistance.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Tolga Aslana, Asli Yenenler-Kutlu, Umut Gerlevik, Ayse Cigdem Aktuglu Zeybek, Ertugrul Kiykim, Osman Ugur Sezermanb, Necla Birgul Iyisona
Summary: Phenylketonuria is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase gene. Two novel mutations in the PAH gene, p.Y198N and p.Y204F, were found in a PKU patient. In-silico analyses and molecular dynamics simulations were used to investigate the impact of these mutations on the structural stability of the PAH enzyme. Results showed that these mutations may affect the spatial organization of catalytic residues and lead to fluctuations in the enzyme structure, potentially inhibiting dimerization and enzyme activation. Further studies are needed to fully understand the roles of these mutations in the etiology of PKU.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Biochemistry & Molecular Biology
Martin Audet, Raymond C. Stevens
Article
Biochemistry & Molecular Biology
Xiaoting Li, Tian Hua, Kiran Vemuri, Jo-Hao Ho, Yiran Wu, Lijie Wu, Petr Popov, Othman Benchama, Nikolai Zvonok, K'ara Locke, Lu Qu, Gye Won Han, Malliga R. Iyer, Resat Cinar, Nathan J. Coffey, Jingjing Wang, Meng Wu, Vsevolod Katritch, Suwen Zhao, George Kunos, Laura M. Bohn, Alexandros Makriyannis, Raymond C. Stevens, Zhi-Jie Liu
Meeting Abstract
Biophysics
Kate L. White, Jitin Singla, John Francis, Jian-Hua Chen, Axel Ekman, Carolyn Larabell, Raymond C. Stevens
BIOPHYSICAL JOURNAL
(2019)
Meeting Abstract
Biophysics
Raymond C. Stevens
BIOPHYSICAL JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Min Xu, Jitin Singla, Elitza Tocheva, Yi-Wei Chang, Raymond C. Stevens, Grant J. Jensen, Frank Alber
Editorial Material
Biochemistry & Molecular Biology
Suwen Zhao, Beili Wu, Raymond C. Stevens
Correction
Multidisciplinary Sciences
Benjamin Stauch, Linda C. Johansson, John D. McCorvy, Nilkanth Patel, Gye Won Han, Xi-Ping Huang, Cornelius Gati, Alexander Batyuk, Samuel T. Slocum, Andrii Ishchenko, Wolfgang Brehm, Thomas A. White, Nairie Michaelian, Caleb Madsen, Lan Zhu, Thomas D. Grant, Jessica M. Grandner, Anna Shiriaeva, Reid H. J. Olsen, Alexandra R. Tribo, Said Yous, Raymond C. Stevens, Uwe Weierstall, Vsevolod Katritch, Bryan L. Roth, Wei Liu, Vadim Cherezov
Article
Biochemistry & Molecular Biology
Jack C. Li, Fariborz Nastertorabi, Weimin Xuan, Gye Won Han, Raymond C. Stevens, Peter G. Schultz
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemical Research Methods
Martin Audet, Kelly Villers, Jeffrey Velasquez, Meihua Chu, Chris Hanson, Raymond C. Stevens
Article
Multidisciplinary Sciences
Xianjun Zhang, Stephen D. Carter, Jitin Singla, Kate L. White, Peter C. Butler, Raymond C. Stevens, Grant J. Jensen
Article
Biochemistry & Molecular Biology
Jitin Singla, Kate L. White, Raymond C. Stevens, Frank Alber
Summary: Cryo-electron tomography allows for unsupervised discovery of endogenous complexes, but assessing the quality of aligned subtomogram clusters with scoring functions can be sensitive to signal-to-noise ratio. Spectral SNR-based Fourier Shell Correlation and Pearson Correlation are robust scoring functions for template-free clustering, with the former being faster for handling large numbers of subtomograms.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jitin Singla, Kylie Burdsall, Brian Cantrell, Jordan R. Halsey, Alex McDowell, Colleen McGregor, Sanraj Mittal, Raymond C. Stevens, Shaoyu Su, Alexandra Thomopoulos, Theotime Vaillant, Kate L. White, Bryan Zhang, Helen M. Berman
Summary: As part of a project, a spatiotemporal model of the pancreatic b-cell is being built and an immersive experience called World in a Cell is being created for integrating and generating new educational tools. A new visual design language using tetrahedral building blocks has been developed to represent the structural features of biological molecules and organelles in crowded cellular environments, enabling more efficient animation and user interaction in the immersive environment.
Article
Genetics & Heredity
Cristina Segovia-Falquina, Alicia Vilas, Fatima Leal, Francisco del Cano-Ochoa, Edwin P. Kirk, Magdalena Ugarte, Santiago Ramon-Maiques, Alejandra Gamez, Belen Perez
Summary: This study investigates the expression, stability, and enzymatic properties of PMM2 variants, including novel ones, in order to explore the potential use of pharmacochaperones in treating PMM2-CDG. The results show that some variants can be effectively rescued by pharmacochaperoning treatment, providing a new approach for clinical treatment.
Article
Chemistry, Organic
Dongxiang Xue, Lintao Ye, Jun Zheng, Yiran Wu, Xianjun Zhang, Yueming Xu, Tao Li, Raymond C. Stevens, Fei Xu, Min Zhuang, Suwen Zhao, Fei Zhao, Houchao Tao
ORGANIC & BIOMOLECULAR CHEMISTRY
(2019)
Article
Chemistry, Multidisciplinary
M. Gertrude Gutierrez, Jacob Deyell, Kate L. White, Lucia C. Dalle Ore, Vadim Cherezov, Raymond C. Stevens, Noah Malmstadt
CHEMICAL COMMUNICATIONS
(2019)