scholarly journals Glucose 6-phosphate dehydrogenase mutations causing enzyme deficiency in a model of the tertiary structure of the human enzyme

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2974-2982 ◽  
Author(s):  
CE Naylor ◽  
P Rowland ◽  
AK Basak ◽  
S Gover ◽  
PJ Mason ◽  
...  
Keyword(s):  
Tertiary Structure ◽  
Clinical Symptoms ◽  
Enzyme Stability ◽  
Three Dimensional ◽  
Point Mutations ◽  
Clinical Manifestations ◽  
Enzyme Deficiency ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Glucose 6 Phosphate Dehydrogenase

Human glucose 6-phosphate dehydrogenase (G6PD) has a particularly large number of variants resulting from point mutations; some 60 mutations have been sequenced to date. Many variants, some polymorphic, are associated with enzyme deficiency. Certain variants have severe clinical manifestations; for such variants, the mutant enzyme almost always displays a reduced thermal stability. A homology model of human G6PD has been built, based on the three-dimensional structure of the enzyme from Leuconostoc mesenteroides. The model has suggested structural reasons for the diminished enzyme stability and hence for deficiency. It has shown that a cluster of mutations in exon 10, resulting in severe clinical symptoms, occurs at or near the dimer interface of the enzyme, that the eight-residue deletion in the variant Nara is at a surface loop, and that the two mutations in the A- variant are close together in the three-dimensional structure.

scholarly journals Construction of A Preliminary Three-Dimensional Structure Simian betaretrovirus Serotype-2 (SRV-2) Reverse Transcriptase Isolated from Indonesian Cynomolgus Monkey

2020 ◽  
Vol 31 (3) ◽  
pp. 47-61
Author(s):  
Uus Saepuloh ◽  
Diah Iskandriati ◽  
Joko Pamungkas ◽  
Dedy Duryadi Solihin ◽  
Sela Septima Mariya ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Cynomolgus Monkey ◽  
Tertiary Structure ◽  
Vaccine Development ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Nucleotide Position ◽  
Structure Model ◽  
Three Dimensional Structure ◽  
Hiv 1

Simian betaretrovirus serotype-2 (SRV-2) is an important pathogenic agent in Asian macaques. It is a potential confounding variable in biomedical research. SRV-2 also provides a valuable viral model compared to other retroviruses which can be used for understanding many aspects of retroviral-host interactions and immunosuppression, infection mechanism, retroviral structure, antiretroviral and vaccine development. In this study, we isolated the gene encoding reverse transcriptase enzyme (RT) of SRV-2 that infected Indonesian cynomolgus monkey (Mf ET1006) and predicted the three dimensional structure model using the iterative threading assembly refinement (I-TASSER) computational programme. This SRV-2 RT Mf ET1006 consisted of 547 amino acids at nucleotide position 3284–4925 of whole genome SRV-2. The polymerase active site located in the finger/palm subdomain characterised by three conserved catalytic aspartates (Asp90, Asp165, Asp166), and has a highly conserved YMDD motif as Tyr163, Met164, Asp165 and Asp166. We estimated that this SRV-2 RT Mf ET1006 structure has the accuracy of template modelling score (TM-score 0.90 ± 0.06) and root mean square deviation (RMSD) 4.7 ± 3.1Å, indicating that this model can be trusted and the accuracy can be seen from the appearance of protein folding in tertiary structure. The superpositionings between SRV-2 RT Mf ET1006 and Human Immunodeficiency Virus-1 (HIV-1) RT were performed to predict the structural in details and to optimise the best fits for illustrations. This SRV-2 RT Mf ET1006 structure model has the highest homology to HIV-1 RT (2B6A.pdb) with estimated accuracy at TM-score 0.911, RMSD 1.85 Å, and coverage of 0.953. This preliminary study of SRV-2 RT Mf ET1006 structure modelling is intriguing and provide some information to explore the molecular characteristic and biochemical mechanism of this enzyme.

scholarly journals Efficient targeting to storage granules of human proinsulins with altered propeptide domain.

1988 ◽  
Vol 106 (6) ◽  
pp. 1843-1851 ◽  
Author(s):  
S K Powell ◽  
L Orci ◽  
C S Craik ◽  
H P Moore
Keyword(s):  
High Efficiency ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Structural Domains ◽  
C Peptide ◽  
Three Dimensional Structure ◽  
Morphological Criteria ◽  
Cellular Machinery ◽  
Storage Granules

In neuronal and endocrine cells, peptide hormones are selectively segregated into storage granules, while other proteins are exported continuously without storage. Sorting of hormones by cellular machinery involves the recognition of specific structural domains on prohormone molecules. Since the propeptide of insulin is known to play an important role in its three-dimensional structure, it is reasonable to speculate that targeting of proinsulin to storage granules would require a functional connecting peptide. To test this hypothesis, we constructed two mutations in human proinsulin with different predicted structures. In one mutation, Ins delta C, the entire C peptide was deleted, resulting in an altered insulin in which the B and the A chains are joined contiguously. In the other mutation, Ins/IGF, the C peptide of proinsulin was replaced with the unrelated 12-amino acid connecting peptide of human insulin-like growth factor-I; this substitution should permit correct folding of the B and A chains to form a tertiary structure similar to that of proinsulin. By several biochemical and morphological criteria, we found that Ins/IGF is efficiently targeted to storage granules, suggesting that the C peptide of proinsulin does not contain necessary sorting information. Unexpectedly, Ins delta C, which presumably cannot fold properly, is also targeted to granules at a high efficiency. These results imply that either the targeting machinery can tolerate changes in the tertiary structure of transported proteins, or that the B and A chains of insulin can form a relatively intact three-dimensional structure even in the absence of C peptide.

Synopses from the poster exhibition organized by I. M. Kerr, 1. Interferon: a tertiary structure predicted from amino acid sequences

1982 ◽  
Vol 299 (1094) ◽  
pp. 125-127 ◽  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
X Ray ◽  
Three Dimensional Structure ◽  
X Ray Crystallography ◽  
Functional Studies

Functional studies on interferon would be helped by a three-dimensional structure for the molecule. However, it may be several years before the structure of the protein is determined by X-ray crystallography. We have therefore used available methods for predicting the secondary - and the tertiary - structure of a protein from its amino acid sequence to propose a tertiary model involving the packing of four a-helices. Details of this work have been published elsewhere (Sternberg & Cohen 1982).

scholarly journals Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure

2003 ◽  
Vol 376 (1) ◽  
pp. 97-107 ◽  
Author(s):  
Philipp NEUDECKER ◽  
Katrin LEHMANN ◽  
Jörg NERKAMP ◽  
Tanja HAASE ◽  
Andrea WANGORSCH ◽  
...  
Keyword(s):  
Prunus Avium ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Apium Graveolens ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Bet V 1 ◽  
Ige Reactivity ◽  
Ige Binding ◽  
Ige Epitope

Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155–159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy.

Modeling the impact of point mutations on the stability of proteins

2020 ◽  
Vol 18 (04) ◽  
pp. 2050019
Author(s):  
K. G. Kulikov ◽  
T. V. Koshlan
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Point Mutations ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Three Dimensional Structure ◽  
The Stability ◽  
The Impact ◽  
Proven Theorem

A new method has been introduced which allows us to determine the stability of protein complexes with point changes of amino acid residues that also take into account the three-dimensional structure of the complex. This formulated and proven theorem is aimed at determining the criterion for the stability of protein molecules. The algorithm and software package were developed for analyzing protein interactions, taking into account their three-dimensional structure from the PDB database.

The Three-dimensional structure of frozen-hydrated nudaurelia capensis β virus

1987 ◽  
Vol 45 ◽  
pp. 650-651
Author(s):  
N. H. Olson ◽  
T. S. Baker ◽  
Wu Bo Mu ◽  
J. E. Johnson ◽  
D. A. Hendry
Keyword(s):  
South African ◽  
Rna Virus ◽  
Carbon Film ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Electron Dose ◽  
Total Electron ◽  
Three Dimensional Structure ◽  
Negative Stain ◽  
Dimensional Reconstruction

Nudaurelia capensis β virus (NβV) is an RNA virus of the South African Pine Emperor moth, Nudaurelia cytherea capensis (Lepidoptera: Saturniidae). The NβV capsid is a T = 4 icosahedron that contains 60T = 240 subunits of the coat protein (Mr = 61,000). A three-dimensional reconstruction of the NβV capsid was previously computed from visions embedded in negative stain suspended over holes in a carbon film. We have re-examined the three-dimensional structure of NβV, using cryo-microscopy to examine the native, unstained structure of the virion and to provide a initial phasing model for high-resolution x-ray crystallographic studiesNβV was purified and prepared for cryo-microscopy as described. Micrographs were recorded ∼1 - 2 μm underfocus at a magnification of 49,000X with a total electron dose of about 1800 e-/nm2.

Three Dimensional structure and organization of diploid chromosomes by optical section microscopy

1987 ◽  
Vol 45 ◽  
pp. 633-635
Author(s):  
David A. Agard ◽  
Yasushi Hiraoka ◽  
John W. Sedat
Keyword(s):  
Dimensional Space ◽  
Three Dimensional ◽  
Developmental State ◽  
Mitotic Cell ◽  
Biological Properties ◽  
Dimensional Structure ◽  
Specific Gene ◽  
Three Dimensional Structure ◽  
Complementary Techniques ◽  
Dynamic Structures

In an effort to understand the complex relationship between structure and biological function within the nucleus, we have embarked on a program to examine the three-dimensional structure and organization of Drosophila melanogaster embryonic chromosomes. Our overall goal is to determine how DNA and proteins are organized into complex and highly dynamic structures (chromosomes) and how these chromosomes are arranged in three dimensional space within the cell nucleus. Futher, we hope to be able to correlate structual data with such fundamental biological properties as stage in the mitotic cell cycle, developmental state and transcription at specific gene loci.Towards this end, we have been developing methodologies for the three-dimensional analysis of non-crystalline biological specimens using optical and electron microscopy. We feel that the combination of these two complementary techniques allows an unprecedented look at the structural organization of cellular components ranging in size from 100A to 100 microns.

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