scholarly journals Interaction of human neutrophil flavocytochrome b with cytosolic proteins: transferred-NOESY NMR studies of a gp91phox C-terminal peptide bound to p47phox

1997 ◽  
Vol 325 (1) ◽  
pp. 249-257 ◽  
Author(s):  
Earle R. ADAMS ◽  
Edward A. DRATZ ◽  
Dawit GIZACHEW ◽  
Frank R. DeLEO ◽  
Lixin YU ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nadph Oxidase ◽  
Nuclear Overhauser Effect ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Side Chains ◽  
Nmr Studies ◽  
C Terminus ◽  
Amino Acid Side Chains ◽  
Flavocytochrome B

During activation of the neutrophil NADPH oxidase, cytosolic p47phox is translocated to the membrane where it associates with flavocytochrome b via multiple binding regions, including a site in the C-terminus of gp91phox. To investigate this binding site further, we studied the three-dimensional structure of a gp91phox C-terminal peptide (551SNSESGPRGVHFIFNKEN568) bound to p47phox using transferred nuclear Overhauser effect spectroscopy (Tr-NOESY) NMR. Using MARDIGRAS analysis and simulated annealing, five similar sets of structures of the p47phox-bound peptide were obtained, all containing an extended open bend from Ser5 to Phe14 (corresponding to gp91phox residues 555–564). The ends of the peptide were poorly defined, however, suggesting they were more flexible. Therefore further refinement was performed on the Ser5–Phe14 region of the peptide after omitting the ends of the peptide from consideration. In this case, two similar structures were obtained. Both structures again exhibited extended open-bend conformations. In addition, the amino acid side chains that showed evidence of immobilization on binding to p47phox correlated directly with those that were found previously to be essential for biological activity. Thus during NADPH oxidase assembly, the C-terminus of gp91phox binds to 47phox in an extended conformation between gp91phox residues 555 and 564, with immobilization of all of the amino acid side chains in the 558RGVHFIF564 region except for His561.

The three-dimensional structure of crystalline porcine pancreatic elastase

1970 ◽  
Vol 257 (813) ◽  
pp. 111-118 ◽  
Keyword(s):  
Amino Acid ◽  
Catalytic Mechanism ◽  
Polypeptide Chain ◽  
Molecular Model ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Side Chains ◽  
Peptide Bonds ◽  
Single Polypeptide Chain ◽  
Single Polypeptide

Elastase is a proteolytic enzyme obtained from pig pancreas, which shows a high degree of amino acid sequence homology with other serine proteinases, including bovine trypsin and chymotrypsin (Hartley, this volume, p. 77). It consists of a single polypeptide chain of 240 residues, which corresponds to the single polypeptide chain of trypsin, and the B and C chains of chymotrypsin. Elastase possesses a common catalytic mechanism with these enzymes but differs from them in its substrate specificity, cleaving peptide bonds on the carboxyl terminal side of amino acid residues lacking charged or aromatic side chains (Naughton & Sanger 1961). Several workers have suggested that homologous enzymes with common catalytic mechanisms have very similar tertiary structures. This prediction was supported by Blow and his co-workers, who found that the two disulphide bridges present in trypsin, but absent in chymotrypsin, could be built into the molecular model of a-chymotrypsin with little or no distortion of the polypeptide chain (Sigler, Blow, Matthews & Henderson 1968), and by Hartley (this volume, p. 77) who has shown that the trypsin and elastase side chains can be substituted for those present in a skeletal molecular model of a-chymotrypsin with no gross distortions of the polypeptide chain.

A Graph-theoretic Approach to the Identification of Three-dimensional Patterns of Amino Acid Side-chains in Protein Structures

1994 ◽  
Vol 243 (2) ◽  
pp. 327-344 ◽  
Author(s):  
Peter J. Artymiuk ◽  
Andrew R. Poirrette ◽  
Helen M. Grindley ◽  
David W. Rice ◽  
Peter Willett
Keyword(s):  
Amino Acid ◽  
Protein Structures ◽  
Three Dimensional ◽  
Side Chains ◽  
Theoretic Approach ◽  
Graph Theoretic ◽  
Graph Theoretic Approach ◽  
Amino Acid Side Chains

Predicting the Strength of Stacking Interactions Between Heterocycles and Aromatic Amino Acid Side Chains

2019 ◽  
Author(s):  
Andrea N. Bootsma ◽  
Analise C. Doney ◽  
Steven Wheeler
Keyword(s):  
Amino Acid ◽  
Binding Sites ◽  
Aromatic Amino Acid ◽  
Aromatic Amino Acids ◽  
Biologically Active ◽  
Side Chains ◽  
Stacking Interactions ◽  
Inhibitor Binding ◽  
Protein Binding Sites ◽  
Amino Acid Side Chains

<p>Despite the ubiquity of stacking interactions between heterocycles and aromatic amino acids in biological systems, our ability to predict their strength, even qualitatively, is limited. Based on rigorous <i>ab initio</i> data, we have devised a simple predictive model of the strength of stacking interactions between heterocycles commonly found in biologically active molecules and the amino acid side chains Phe, Tyr, and Trp. This model provides rapid predictions of the stacking ability of a given heterocycle based on readily-computed heterocycle descriptors. We show that the values of these descriptors, and therefore the strength of stacking interactions with aromatic amino acid side chains, follow simple predictable trends and can be modulated by changing the number and distribution of heteroatoms within the heterocycle. This provides a simple conceptual model for understanding stacking interactions in protein binding sites and optimizing inhibitor binding in drug design.</p>

A Strategy for Thioamide Incorporation During Fmoc Solid-Phase Peptide Synthesis with Robust Stereochemical Integrity

2019 ◽  
Author(s):  
luis camacho III ◽  
Bryan J. Lampkin ◽  
Brett VanVeller
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Side Chains ◽  
Amino Acid Side Chains ◽  
Peptide Elongation

We describe a method to protect the sensitive stereochemistry of the thioamide—in analogy to the protection of the functional groups of amino acid side chains—in order to preserve the thioamide moiety during peptide elongation.<br>

scholarly journals Structural analysis of mutations in the Drosophila beta 2-tubulin isoform reveals regions in the beta-tubulin molecular required for general and for tissue-specific microtubule functions.

Genetics ◽  
1995 ◽  
Vol 139 (1) ◽  
pp. 267-286 ◽  
Author(s):  
J D Fackenthal ◽  
J A Hutchens ◽  
F R Turner ◽  
E C Raff
Keyword(s):  
Amino Acid ◽  
Three Dimensional ◽  
Variable Region ◽  
Internal Variable ◽  
Microtubule Assembly ◽  
Dimensional Structure ◽  
Wild Type ◽  
Beta Tubulin ◽  
Assembly Kinetics ◽  
Beta 2

Abstract We have determined the lesions in a number of mutant alleles of beta Tub85D, the gene that encodes the testis-specific beta 2-tubulin isoform in Drosophila melanogaster. Mutations responsible for different classes of functional phenotypes are distributed throughout the beta 2-tubulin molecule. There is a telling correlation between the degree of phylogenetic conservation of the altered residues and the number of different microtubule categories disrupted by the lesions. The majority of lesions occur at positions that are evolutionarily highly conserved in all beta-tubulins; these lesions disrupt general functions common to multiple classes of microtubules. However, a single allele B2t6 contains an amino acid substitution within an internal cluster of variable amino acids that has been identified as an isotype-defining domain in vertebrate beta-tubulins. Correspondingly, B2t6 disrupts only a subset of microtubule functions, resulting in misspecification of the morphology of the doublet microtubules of the sperm tail axoneme. We previously demonstrated that beta 3, a developmentally regulated Drosophila beta-tubulin isoform, confers the same restricted morphological phenotype in a dominant way when it is coexpressed in the testis with wild-type beta 2-tubulin. We show here by complementation analysis that beta 3 and the B2t6 product disrupt a common aspect of microtubule assembly. We therefore conclude that the amino acid sequence of the beta 2-tubulin internal variable region is required for generation of correct axoneme morphology but not for general microtubule functions. As we have previously reported, the beta 2-tubulin carboxy terminal isotype-defining domain is required for suprastructural organization of the axoneme. We demonstrate here that the beta 2 variant lacking the carboxy terminus and the B2t6 variant complement each other for mild-to-moderate meiotic defects but do not complement for proper axonemal morphology. Our results are consistent with the hypothesis drawn from comparisons of vertebrate beta-tubulins that the two isotype-defining domains interact in a three-dimensional structure in wild-type beta-tubulins. We propose that the integrity of this structure in the Drosophila testis beta 2-tubulin isoform is required for proper axoneme assembly but not necessarily for general microtubule functions. On the basis of our observations we present a model for regulation of axoneme microtubule morphology as a function of tubulin assembly kinetics.

scholarly journals Mobile unnatural amino acid side chains in the core of staphylococcal nuclease

1996 ◽  
Vol 5 (6) ◽  
pp. 1026-1031 ◽  
Author(s):  
Richard Wynn ◽  
Paul C. Harkins ◽  
Frederic M. Richards ◽  
Robert O. Fox
Keyword(s):  
Amino Acid ◽  
Staphylococcal Nuclease ◽  
Unnatural Amino Acid ◽  
Side Chains ◽  
The Core ◽  
Amino Acid Side Chains

scholarly journals Intrinsic Energy Landscapes of Amino Acid Side-Chains

2012 ◽  
Vol 52 (6) ◽  
pp. 1559-1572 ◽  
Author(s):  
Xiao Zhu ◽  
Pedro E.M. Lopes ◽  
Jihyun Shim ◽  
Alexander D. MacKerell
Keyword(s):  
Amino Acid ◽  
Side Chains ◽  
Energy Landscapes ◽  
Amino Acid Side Chains ◽  
Intrinsic Energy
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