scholarly journals Structural and molecular basis for the novel catalytic mechanism and evolution of DddP , an abundant peptidase‐like bacterial Dimethylsulfoniopropionate lyase: a new enzyme from an old fold

2015 ◽  
Vol 98 (2) ◽  
pp. 289-301 ◽  
Author(s):  
Peng Wang ◽  
Xiu‐Lan Chen ◽  
Chun‐Yang Li ◽  
Xiang Gao ◽  
De‐yu Zhu ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Catalytic Mechanism ◽  
The Novel

scholarly journals Molecular Basis of Sulfonamide and Trimethoprim Resistance in Fish-Pathogenic Aeromonas Isolates

2011 ◽  
Vol 77 (20) ◽  
pp. 7147-7150 ◽  
Author(s):  
Kristina Kadlec ◽  
Ellen von Czapiewski ◽  
Heike Kaspar ◽  
Jürgen Wallmann ◽  
Geovana Brenner Michael ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Molecular Basis ◽  
Aeromonas Salmonicida ◽  
The Novel ◽  
Content Type ◽  
Gene Cassettes ◽  
Class 1 Integrons ◽  
Novel Gene ◽  
Class 1 ◽  
Diseased Fish

ABSTRACTSulfonamide-trimethoprim-resistantAeromonas salmonicidaand motileAeromonasspp. from diseased fish of the GERM-Vet study carried thesul1gene together with mostly cassette-borne trimethoprim resistance genes, including the novel genedfrA28. The sevendfrAanddfrBgenes identified were located mostly in class 1 integrons which commonly harbored other gene cassettes.

Why does tautomycetin thioesterase prefer hydrolysis to macrocyclization? Theoretical study on its catalytic mechanism

2019 ◽  
Vol 9 (22) ◽  
pp. 6391-6403
Author(s):  
Lei Liu ◽  
Wentao Tao ◽  
Linquan Bai ◽  
Eung-Soo Kim ◽  
Yi-Lei Zhao ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Catalytic Mechanism ◽  
Theoretical Study

In this study, we attempted to uncover the reasons why Tautomycetin thioesterase (TMC TE) prefers hydrolysis rather than macrocyclization, and reveal the molecular basis of TE-catalyzed hydrolysis and macrocyclization.

Insights into the binding specificity and catalytic mechanism ofN-acetylhexosamine 1-phosphate kinases through multiple reaction complexes

2014 ◽  
Vol 70 (5) ◽  
pp. 1401-1410 ◽  
Author(s):  
Kuei-Chen Wang ◽  
Syue-Yi Lyu ◽  
Yu-Chen Liu ◽  
Chin-Yuan Chang ◽  
Chang-Jer Wu ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Catalytic Mechanism ◽  
Structural Information ◽  
Bifidobacterium Longum ◽  
Three Dimensional ◽  
Binding Specificity ◽  
Chemoenzymatic Synthesis ◽  
Leloir Pathway ◽  
The Given

Utilization ofN-acetylhexosamine in bifidobacteria requires the specific lacto-N-biose/galacto-N-biose pathway, a pathway differing from the Leloir pathway while establishing symbiosis between humans and bifidobacteria. The genelnpBin the pathway encodes a novel hexosamine kinase NahK, which catalyzes the formation ofN-acetylhexosamine 1-phosphate (GlcNAc-1P/GalNAc-1P). In this report, seven three-dimensional structures of NahK in complex with GlcNAc, GalNAc, GlcNAc-1P, GlcNAc/AMPPNP and GlcNAc-1P/ADP from bothBifidobacterium longum(JCM1217) andB. infantis(ATCC15697) were solved at resolutions of 1.5–2.2 Å. NahK is a monomer in solution, and its polypeptide folds in a crescent-like architecture subdivided into two domains by a deep cleft. The NahK structures presented here represent the first multiple reaction complexes of the enzyme. This structural information reveals the molecular basis for the recognition of the given substrates and products, GlcNAc/GalNAc, GlcNAc-1P/GalNAc-1P, ATP/ADP and Mg2+, and provides insights into the catalytic mechanism, enabling NahK and mutants thereof to form a choice of biocatalysts for enzymatic and chemoenzymatic synthesis of carbohydrates.

scholarly journals Molecular basis of titin exon exclusion by RBM20 and the novel titin splice regulator PTB4

2018 ◽  
Vol 46 (10) ◽  
pp. 5227-5238 ◽  
Author(s):  
Vita Dauksaite ◽  
Michael Gotthardt
Keyword(s):  
Molecular Basis ◽  
The Novel ◽  
Splice Regulator

Primary Aldosteronism: Novel Insights

2020 ◽  
Vol 16 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Konstantinos Stavropoulos ◽  
Konstantinos Imprialos ◽  
Vasilios Papademetriou ◽  
Charles Faselis ◽  
Kostas Tsioufis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Primary Aldosteronism ◽  
Molecular Basis ◽  
Diagnostic Procedure ◽  
Secondary Hypertension ◽  
Future Research ◽  
The Novel ◽  
Future Perspectives ◽  
Common Causes ◽  
Existing Data

Background: Primary aldosteronism is one of the most common causes of secondary hypertension. Patients with this endocrine syndrome are at increased cardiovascular risk, higher than hypertensive individuals with equal blood pressure levels. Objectives: The study aimed to thoroughly present and critically discuss the novel insights into the field of primary aldosteronism, focusing on the clinically meaningful aspects. Method: We meticulously evaluated existing data in the field of primary aldosteronism in order to summarize future perspectives in this narrative review. Results: Novel data suggests that a subclinical form of primary aldosteronism might exist. Interesting findings might simplify the diagnostic procedure of the disease, especially for the localization of primary aldosteronism. The most promising progress has been noted in the field of the molecular basis of the disease, suggesting new potential therapeutic targets. Conclusion: Several significant aspects are at early stages of evaluation. Future research is essential to investigate these well-promising perspectives.

scholarly journals A DNA sequence conferring high postmeiotic segregation frequency to heterozygous deletions in Saccharomyces cerevisiae is related to sequences associated with eucaryotic recombination hotspots.

1988 ◽  
Vol 8 (3) ◽  
pp. 1253-1258 ◽  
Author(s):  
J H White ◽  
J F DiMartino ◽  
R W Anderson ◽  
K Lusnak ◽  
D Hilbert ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Basis ◽  
The Novel ◽  
Joint Region ◽  
Base Pairs ◽  
Deletion Mutations ◽  
Recombination Hotspots ◽  
Postmeiotic Segregation ◽  
Human And Mouse ◽  
Common Sequence

The meiotic behavior of two graded series of deletion mutations in the ADE8 gene in Saccharomyces cerevisiae was analyzed to investigate the molecular basis of meiotic recombination. Postmeiotic segregation (PMS) was observed for a subset of the deletion heterozygosities, including deletions of 38 to 93 base pairs. There was no clear relationship between deletion length and PMS frequency. A common sequence characterized the novel joint region in the alleles which displayed PMS. This sequence is related to repeated sequences recently identified in association with recombination hotspots in the human and mouse genomes. We propose that these particular deletion heterozygosities escape heteroduplex DNA repair because of fortuitous homology to a binding site for a protein.

PLP undergoes conformational changes during the course of an enzymatic reaction

2014 ◽  
Vol 70 (2) ◽  
pp. 596-606 ◽  
Author(s):  
Ho-Phuong-Thuy Ngo ◽  
Nuno M. F. S. A. Cerqueira ◽  
Jin-Kwang Kim ◽  
Myoung-Ki Hong ◽  
Pedro Alexandrino Fernandes ◽  
...  
Keyword(s):  
Conformational Change ◽  
Conformational Changes ◽  
Catalytic Mechanism ◽  
Enzymatic Reaction ◽  
Nucleophilic Attack ◽  
The Novel ◽  
X Ray ◽  
X Ray Crystallography ◽  
Starting Point ◽  
High Level

Numerous enzymes, such as the pyridoxal 5′-phosphate (PLP)-dependent enzymes, require cofactors for their activities. Using X-ray crystallography, structural snapshots of the L-serine dehydratase catalytic reaction of a bacterial PLP-dependent enzyme were determined. In the structures, the dihedral angle between the pyridine ring and the Schiff-base linkage of PLP varied from 18° to 52°. It is proposed that the organic cofactor PLP directly catalyzes reactions by active conformational changes, and the novel catalytic mechanism involving the PLP cofactor was confirmed by high-level quantum-mechanical calculations. The conformational change was essential for nucleophilic attack of the substrate on PLP, for concerted proton transfer from the substrate to the protein and for directing carbanion formation of the substrate. Over the whole catalytic cycle, the organic cofactor catalyzes a series of reactions, like the enzyme. The conformational change of the PLP cofactor in catalysis serves as a starting point for identifying the previously unknown catalytic roles of organic cofactors.

The crystal structure of Thermotoga maritima maltosyltransferase and its implications for the molecular basis of the novel transfer specificity 1 1Edited by R. Huber

2001 ◽  
Vol 312 (1) ◽  
pp. 119-131 ◽  
Author(s):  
Anna Roujeinikova ◽  
Carsten Raasch ◽  
Jacky Burke ◽  
Patrick J Baker ◽  
Wolfgang Liebl ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Basis ◽  
Thermotoga Maritima ◽  
The Novel

scholarly journals Novel MYO1D Missense Variant Identified Through Whole Exome Sequencing and Computational Biology Analysis Expands the Spectrum of Causal Genes of Laterality Defects

2021 ◽  
Vol 8 ◽  
Author(s):  
Rabab Said Alsafwani ◽  
Khalidah K. Nasser ◽  
Thoraia Shinawi ◽  
Babajan Banaganapalli ◽  
Hanan Abdelhalim ElSokary ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Developmental Disorders ◽  
Personalised Medicine ◽  
Missense Variant ◽  
High Rate ◽  
The Novel ◽  
Arab Population ◽  
Protein Variant ◽  
Left Isomerism ◽  
Laterality Defects

Laterality defects (LDs) or asymmetrically positioned organs are a group of rare developmental disorders caused by environmental and/or genetic factors. However, the exact molecular pathophysiology of LD is not yet fully characterised. In this context, studying Arab population presents an ideal opportunity to discover the novel molecular basis of diseases owing to the high rate of consanguinity and genetic disorders. Therefore, in the present study, we studied the molecular basis of LD in Arab patients, using next-generation sequencing method. We discovered an extremely rare novel missense variant in MYO1D gene (Pro765Ser) presenting with visceral heterotaxy and left isomerism with polysplenia syndrome. The proband in this index family has inherited this homozygous variant from her heterozygous parents following the autosomal recessive pattern. This is the first report to show MYO1D genetic variant causing left–right axis defects in humans, besides previous known evidence from zebrafish, frog and Drosophila models. Moreover, our multilevel bioinformatics-based structural (protein variant structural modelling, divergence, and stability) analysis has suggested that Ser765 causes minor structural drifts and stability changes, potentially affecting the biophysical and functional properties of MYO1D protein like calmodulin binding and microfilament motor activities. Functional bioinformatics analysis has shown that MYO1D is ubiquitously expressed across several human tissues and is reported to induce severe phenotypes in knockout mouse models. In conclusion, our findings show the expanded genetic spectrum of LD, which could potentially pave way for the novel drug target identification and development of personalised medicine for high-risk families.

scholarly journals Transcriptomic and functional analysis of the oosome, a unique form of germ plasm in the waspNasonia vitripennis

2018 ◽  
Author(s):  
Honghu Quan ◽  
Jeremy Lynch
Keyword(s):  
Molecular Basis ◽  
Germ Plasm ◽  
Cell Formation ◽  
Solid Sphere ◽  
The Novel ◽  
Developmental Networks ◽  
Pole Cell ◽  
Polar Granules ◽  
Developmental Role ◽  
Pole Cells

AbstractBackgroundThe oosome is the germline determinant in the waspNasonia vitripennisand is homologous to the polar granules ofDrosophila. Despite a common evolutionary origin and developmental role, the oosome is morphologically quite distinct from polar granules. It is a solid sphere that migrates within the cytoplasm before budding out and forming pole cells.ResultsTo gain an understanding of both the molecular basis of the novel form of the oosome, and the conserved essential features of germ plasm, we quantified and compared transcript levels between embryo fragments that contained the oosome, and those that did not. The identity of the localized transcripts indicated thatNasoniauses different molecules to carry out conserved germ plasm functions. In addition, functional testing of a sample of localized transcripts revealed potentially novel mechanisms of ribonucleoprotein assembly and pole cell cellularization in the wasp.ConclusionsOur results demonstrate that numerous novel and unexpected molecules have been recruited in order produce the unique characteristics of the oosome and pole cell formation inNasonia. This work will serve as the basis for further investigation into the patterns of germline determinant evolution among insects, the molecular basis of extreme morphology of ribonucleoproteins, and the incorporation of novel components into developmental networks.

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