FAD-BERT: Improved prediction of FAD binding sites using pre-training of deep bidirectional transformers

2021 ◽  
Vol 131 ◽  
pp. 104258
Author(s):  
Quang-Thai Ho ◽  
Trinh-Trung-Duong Nguyen ◽  
Nguyen Quoc Khanh Le ◽  
Yu-Yen Ou
Keyword(s):  
Binding Sites ◽  
Fad Binding

scholarly journals Mutation of Aspartate 238 in FAD Synthase Isoform 6 Increases the Specific Activity by Weakening the FAD Binding

2019 ◽  
Vol 20 (24) ◽  
pp. 6203 ◽  
Author(s):  
Piero Leone ◽  
Michele Galluccio ◽  
Stefano Quarta ◽  
Ernesto Anoz-Carbonell ◽  
Milagros Medina ◽  
...  
Keyword(s):  
Binding Sites ◽  
Specific Activity ◽  
Synthesis Rate ◽  
General Increase ◽  
Respiratory Chain Deficiency ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Acyl Coa Dehydrogenases ◽  
Rate Limiting ◽  
Fad Binding

FAD synthase (FADS, or FMN:ATP adenylyl transferase) coded by the FLAD1 gene is the last enzyme in the pathway of FAD synthesis. The mitochondrial isoform 1 and the cytosolic isoform 2 are characterized by the following two domains: the C-terminal PAPS domain (FADSy) performing FAD synthesis and pyrophosphorolysis; the N-terminal molybdopterin-binding domain (FADHy) performing a Co++/K+-dependent FAD hydrolysis. Mutations in FLAD1 gene are responsible for riboflavin responsive and non-responsive multiple acyl-CoA dehydrogenases and combined respiratory chain deficiency. In patients harboring frameshift mutations, a shorter isoform (hFADS6) containing the sole FADSy domain is produced representing an emergency protein. With the aim to ameliorate its function we planned to obtain an engineered more efficient hFADS6. Thus, the D238A mutant, resembling the D181A FMNAT “supermutant” of C. glabrata, was overproduced and purified. Kinetic analysis of this enzyme highlighted a general increase of Km, while the kcat was two-fold higher than that of WT. The data suggest that the FAD synthesis rate can be increased. Additional modifications could be performed to further improve the synthesis of FAD. These results correlate with previous data produced in our laboratory, and point towards the following proposals (i) FAD release is the rate limiting step of the catalytic cycle and (ii) ATP and FMN binding sites are synergistically connected.

scholarly journals Structures and mechanism of the monoamine oxidase family

2011 ◽  
Vol 2 (5) ◽  
pp. 365-377 ◽  
Author(s):  
Helena Gaweska ◽  
Paul F. Fitzpatrick
Keyword(s):  
Monoamine Oxidase ◽  
Binding Sites ◽  
Flavin Adenine Dinucleotide ◽  
Catalytic Reactions ◽  
Secondary Amines ◽  
Binding Domains ◽  
The Family ◽  
Substrate Binding Sites ◽  
Fad Binding ◽  
Methylated Lysine

AbstractMembers of the monoamine oxidase family of flavoproteins catalyze the oxidation of primary and secondary amines, polyamines, amino acids, and methylated lysine side chains in proteins. The enzymes have similar overall structures, with conserved flavin adenine dinucleotide (FAD)-binding domains and varied substrate-binding sites. Multiple mechanisms have been proposed for the catalytic reactions of these enzymes. The present review compares the structures of different members of the family and the various mechanistic proposals.

scholarly journals Predicting Flavin and Nicotinamide Adenine Dinucleotide-Binding Sites in Proteins Using the Fragment Transformation Method

2015 ◽  
Vol 2015 ◽  
pp. 1-13
Author(s):  
Chih-Hao Lu ◽  
Chin-Sheng Yu ◽  
Yu-Feng Lin ◽  
Jin-Yi Chen
Keyword(s):  
Ligand Binding ◽  
Binding Sites ◽  
False Positive Rate ◽  
Data Bank ◽  
Transformation Method ◽  
Computational Method ◽  
Binding Potential ◽  
Binding Residue ◽  
Positive Rate ◽  
Fad Binding

We developed a computational method to identify NAD- and FAD-binding sites in proteins. First, we extracted from the Protein Data Bank structures of proteins that bind to at least one of these ligands. NAD-/FAD-binding residue templates were then constructed by identifying binding residues through the ligand-binding database BioLiP. The fragment transformation method was used to identify structures within query proteins that resembled the ligand-binding templates. By comparing residue types and their relative spatial positions, potential binding sites were identified and a ligand-binding potential for each residue was calculated. Setting the false positive rate at 5%, our method predicted NAD- and FAD-binding sites at true positive rates of 67.1% and 68.4%, respectively. Our method provides excellent results for identifying FAD- and NAD-binding sites in proteins, and the most important is that the requirement of conservation of residue types and local structures in the FAD- and NAD-binding sites can be verified.

scholarly journals Structural comparison of p-hydroxybenzoate hydroxylase (PobA) from Pseudomonas putida with PobA from other Pseudomonas spp. and other monooxygenases

2019 ◽  
Vol 75 (7) ◽  
pp. 507-514
Author(s):  
John T. Lazar ◽  
Ludmilla Shuvalova ◽  
Monica Rosas-Lemus ◽  
Olga Kiryukhina ◽  
Karla J. F. Satchell ◽  
...  
Keyword(s):  
Pseudomonas Putida ◽  
Binding Sites ◽  
Drug Target ◽  
Tetracycline Resistance ◽  
Hydroxybenzoate Hydroxylase ◽  
Substrate Binding Sites ◽  
Key Residues ◽  
Polypeptide Chains ◽  
Β Sheet ◽  
Fad Binding

The crystal structure is reported of p-hydroxybenzoate hydroxylase (PobA) from Pseudomonas putida, a possible drug target to combat tetracycline resistance, in complex with flavin adenine dinucleotide (FAD). The structure was refined at 2.2 Å resolution with four polypeptide chains in the asymmetric unit. Based on the results of pairwise structure alignments, PobA from P. putida is structurally very similar to PobA from P. fluorescens and from P. aeruginosa. Key residues in the FAD-binding and substrate-binding sites of PobA are highly conserved spatially across the proteins from all three species. Additionally, the structure was compared with two enzymes from the broader class of oxygenases: 2-hydroxybiphenyl 3-monooxygenase (HbpA) from P. nitroreducens and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase (MHPCO) from Mesorhizobium japonicum. Despite having only 14% similarity in their primary sequences, pairwise structure alignments of PobA from P. putida with HbpA from P. nitroreducens and MHPCO from M. japonicum revealed local similarities between these structures. Key secondary-structure elements important for catalysis, such as the βαβ fold, β-sheet wall and α12 helix, are conserved across this expanded class of oxygenases.

Conformation of Ribosomes from Escherichia Coli

1974 ◽  
Vol 32 ◽  
pp. 210-211
Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins
Keyword(s):  
Binding Sites ◽  
Ribosomal Proteins ◽  
Fluorescent Dyes ◽  
Protein Biosynthesis ◽  
Three Dimensional ◽  
Spatial Arrangement ◽  
Dimensional Structure ◽  
Complete Understanding ◽  
And Function

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

Electron Probe Analysis of Muscle

1982 ◽  
Vol 40 ◽  
pp. 398-401
Author(s):  
A. V. Somlyo ◽  
H. Shuman ◽  
A. P. Somlyo
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Resting State ◽  
Binding Sites ◽  
Electron Probe ◽  
Frog Skeletal Muscle ◽  
Electron Probe Analysis ◽  
Probe Analysis

Electron probe analysis of frozen dried cryosections of frog skeletal muscle, rabbit vascular smooth muscle and of isolated, hyperpermeab1 e rabbit cardiac myocytes has been used to determine the composition of the cytoplasm and organelles in the resting state as well as during contraction. The concentration of elements within the organelles reflects the permeabilities of the organelle membranes to the cytoplasmic ions as well as binding sites. The measurements of [Ca] in the sarcoplasmic reticulum (SR) and mitochondria at rest and during contraction, have direct bearing on their role as release and/or storage sites for Ca in situ.

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