scholarly journals Structural Basis for New Pattern of Conserved Amino Acid Residues Related to Chitin-binding in the Antifungal Peptide from the Coconut Rhinoceros BeetleOryctes rhinoceros

2003 ◽  
Vol 278 (25) ◽  
pp. 22820-22827 ◽  
Author(s):  
Hikaru Hemmi ◽  
Jun Ishibashi ◽  
Tetsuya Tomie ◽  
Minoru Yamakawa
Keyword(s):  
Amino Acid ◽  
Structural Basis ◽  
Antifungal Peptide ◽  
Amino Acid Residues

Biological Function and Chemistry of Endothelin. A Review

1999 ◽  
Vol 64 (8) ◽  
pp. 1211-1252 ◽  
Author(s):  
Jan Hlaváček ◽  
Renáta Marcová
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Biological Function ◽  
Biological Properties ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Snake Venoms ◽  
Vasoactive Peptides ◽  
Physico Chemical ◽  
Endothelin A

The first part of this review deals with the biosynthesis and a biological function of strongly vasoactive peptides named endothelins (ETs) including vasoactive intestinal contractor. Where it was useful, snake venoms sarafotoxins which are structural endothelin derivatives, were also mentioned. In the second part, an attention is paid to structural basis of the ETs biological activity, with respect to alterations of amino acid residues in the parent peptides modifying the conformation and consequently the physico-chemical and biological properties in corresponding ETs analogs. Special attention is focussed on the area of ETs receptors and their interaction with peptide and non peptide agonists and antagonists, important in designing selective inhibitors of ETs receptors potentially applicable as drugs in a medicine. A review with 182 references.

scholarly journals Human red blood cell Wright antigens: a genetic and evolutionary perspective on glycophorin A-band 3 interaction

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3942-3947 ◽  
Author(s):  
CH Huang ◽  
ME Reid ◽  
SS Xie ◽  
OO Blumenfeld
Keyword(s):  
Amino Acid ◽  
Nonhuman Primates ◽  
Antigen Expression ◽  
Band 3 ◽  
Structural Basis ◽  
Antigenic Structure ◽  
Glycophorin A ◽  
Amino Acid Residues ◽  
Protein Protein Interaction ◽  
Human Red Blood Cells

The Wright (Wra/Wrb) blood group polymorphism is defined by an allelic change (Lys658Glu) in the band 3 protein; nevertheless, the Wrb antigen apparently requires glycophorin A (GPA) for surface presentation. To gain insight into the structural basis for this protein-protein interaction and delineate its relationship with Wrb antigen expression, we investigated GPA and band 3 sequence polymorphisms occurring in rare humans and nonhuman primates. The lack of GPA or amino acid residues 59 through 71 of GPA results in the absence of Wrb from human red blood cells (RBCs) exhibiting the MkMk, En(a-), or MiV phenotype. However, the SAT homozygous cells carried a Glu658 form of band 3 and a hybrid glycophorin with the entire GPA extramembrane domain from residues 1 through 71, yet expressed no Wrb antigen. This finding suggests that formation of the Wrb antigenic structure is dependent on protein folding and that the transmembrane junction of GPA is important in maintaining the required conformation. Comparative analyses of GPA and band 3 homologues led to the identification in the interacting regions of conserved and dispensable amino acid residues that correlated with the Wrb positive or negative status on nonhuman primates. In particular, the chimpanzee RBCs cells expressed Wrb and the Glu658 form of band 3, which is identical to humans, but their GPA contained the Gly rather than Arg residue at position 61. Taken together, the results suggest that (1) Arg61 of GPA and the proposed Arg61-Glu658 charge pair are not crucial for Wrb antigen exhibition and (2) the role of GPA for interaction with band 3, including Glu658, probably involves a number of amino acid residues located in the alpha-helical region and transmembrane junction.

scholarly journals Inferring amino acid interactions underlying protein function

2017 ◽  
Author(s):  
Victor H. Salinas ◽  
Rama Ranganathan
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Structural Basis ◽  
Evolutionary Divergence ◽  
Amino Acid Residues ◽  
Homologous Proteins ◽  
Physical Constraints ◽  
Spatially Distributed ◽  
Statistical Coupling ◽  
Energetic Interactions

Protein function arises from a poorly defined pattern of cooperative energetic interactions between amino acid residues. Strategies for deducing this pattern have been proposed, but lack of benchmark data has limited experimental verification. Here, we extend deep-mutation technologies to enable measurement of many thousands of pairwise amino acid couplings in members of a protein family. The data show that despite great evolutionary divergence, homologous proteins conserve a sparse, spatially distributed network of cooperative interactions between amino acids that underlies function. This pattern is quantitatively captured in the coevolution of amino acid positions, especially as indicated by the statistical coupling analysis (SCA), providing experimental confirmation of the key tenets of this method. This work establishes a clear link between physical constraints on protein function and sequence analysis, enabling a general practical approach for understanding the structural basis for protein function.

Lucimycin, an antifungal peptide from the therapeutic maggot of the common green bottle fly Lucilia sericata

2014 ◽  
Vol 395 (6) ◽  
pp. 649-656 ◽  
Author(s):  
Anne-Kathrin Pöppel ◽  
Aline Koch ◽  
Karl-Heinz Kogel ◽  
Heiko Vogel ◽  
Christian Kollewe ◽  
...  
Keyword(s):  
Amino Acid ◽  
Plant Pathogens ◽  
Functional Characterization ◽  
Lucilia Sericata ◽  
Random Coil ◽  
Binding Motif ◽  
Antifungal Peptide ◽  
Amino Acid Residues ◽  
Green Bottle ◽  
The Common

Abstract We report the identification, cloning, heterologous expression and functional characterization of a novel antifungal peptide named lucimycin from the common green bottle fly Lucilia sericata. The lucimycin cDNA was isolated from a library of genes induced during the innate immune response in L. sericata larvae, which are used as therapeutic maggots. The peptide comprises 77 amino acid residues with a molecular mass of 8.2 kDa and a pI of 6.6. It is predicted to contain a zinc-binding motif and to form a random coil, lacking β-sheets or other secondary structures. Lucimycin was active against fungi from the phyla Ascomycota, Basidiomycota and Zygomycota, in addition to the oomycete Phytophtora parasitica, but it was inactive against bacteria. A mutant version of lucimycin, lacking the four C-terminal amino acid residues, displayed 40-fold lower activity. The activity of lucimycin against a number of highly-destructive plant pathogens could be exploited to produce transgenic crops that are resistant against fungal diseases.

scholarly journals Evolution-Based Functional Decomposition of Proteins

2015 ◽  
Author(s):  
Olivier Rivoire ◽  
Kimberly A. Reynolds ◽  
Rama Ranganathan
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Biological Properties ◽  
Protein Family ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Multiple Sequence ◽  
Global Pattern ◽  
Sector Analysis ◽  
Statistical Coupling

The essential biological properties of proteins - folding, biochemical activities, and the capacity to adapt - arise from the global pattern of interactions between amino acid residues. The statistical coupling analysis (SCA) is an approach to defining this pattern that involves the study of amino acid coevolution in an ensemble of sequences comprising a protein family. This approach indicates a functional architecture within proteins in which the basic units are coupled networks of amino acids termed sectors. This evolution-based decomposition has potential for new understandings of the structural basis for protein function, but requires broad further testing by the scientific community. To facilitate this, we present here the principles and practice of the SCA and introduce new methods for sector analysis in a python-based software package. We show that the pattern of amino acid interactions within sectors is linked to the divergence of functional lineages in a multiple sequence alignment - a model for how sector properties might be differentially tuned in members of a protein family. This work provides new tools for understanding the structural basis for protein function and for generally testing the concept of sectors as the principal functional units of proteins.

scholarly journals THE STRUCTURAL BASIS FOR BINDING OF COMPLEMENT BY IMMUNOGLOBULIN M

1974 ◽  
Vol 140 (4) ◽  
pp. 1117-1121 ◽  
Author(s):  
Mary M. Hurst ◽  
John E. Volanakis ◽  
Raymond B. Hester ◽  
Robert M. Stroud ◽  
J. Claude Bennett
Keyword(s):  
Amino Acid ◽  
Structural Features ◽  
Immunoglobulin M ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Carboxy Terminal ◽  
Insight Into

An insight into the structural features of human IgM that are responsible for its capacity to bind the first component of complement (C) has been obtained by examining the ability of IgM subfragments to bind active C1 (C1). The smallest two fragments found to bind C1 were the major CNBr fragment of the Fc portion of IgM and the CH4 fragment of the carboxy-terminal domain. The smallest fragment which fixes C1 has a disaggregated mol wt of 6,800, consists of 60 residues, and contains no carbohydrate. Structural considerations and sequence overlaps suggest that the amino-terminal side of the CH4 domain (24 amino acid residues) might be responsible for fixing C1.

scholarly journals Gating mechanisms of a natural anion channelrhodopsin

2015 ◽  
Vol 112 (46) ◽  
pp. 14236-14241 ◽  
Author(s):  
Oleg A. Sineshchekov ◽  
Elena G. Govorunova ◽  
Hai Li ◽  
John L. Spudich
Keyword(s):  
Amino Acid ◽  
Positive Charge ◽  
Ion Selectivity ◽  
Channel Gating ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Gating Mechanisms ◽  
Anion Conductance ◽  
Guillardia Theta ◽  
Sensitive Group

Anion channelrhodopsins (ACRs) are a class of light-gated channels recently identified in cryptophyte algae that provide unprecedented fast and powerful hyperpolarizing tools for optogenetics. Analysis of photocurrents generated byGuillardia thetaACR 1 (GtACR1) and its mutants in response to laser flashes showed thatGtACR1 gating comprises two separate mechanisms with opposite dependencies on the membrane voltage and pH and involving different amino acid residues. The first mechanism, characterized by slow opening and fast closing of the channel, is regulated by Glu-68. Neutralization of this residue (the E68Q mutation) specifically suppressed this first mechanism, but did not eliminate it completely at high pH. Our data indicate the involvement of another, yet-unidentified pH-sensitive group X. Introducing a positive charge at the Glu-68 site (the E68R mutation) inverted the channel gating so that it was open in the dark and closed in the light, without altering its ion selectivity. The second mechanism, characterized by fast opening and slow closing of the channel, was not substantially affected by the E68Q mutation, but was controlled by Cys-102. The C102A mutation reduced the rate of channel closing by the second mechanism by ∼100-fold, whereas it had only a twofold effect on the rate of the first. The results show that anion conductance by ACRs has a fundamentally different structural basis than the relatively well studied conductance by cation channelrhodopsins (CCRs), not attributable to simply a modification of the CCR selectivity filter.

scholarly journals Coevolution-based inference of amino acid interactions underlying protein function

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Victor H Salinas ◽  
Rama Ranganathan
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Physical Constraints ◽  
Cooperative Interactions ◽  
Evolutionarily Conserved ◽  
Statistical Coupling ◽  
Energetic Interactions ◽  
Statistical Coupling Analysis

Protein function arises from a poorly understood pattern of energetic interactions between amino acid residues. Sequence-based strategies for deducing this pattern have been proposed, but lack of benchmark data has limited experimental verification. Here, we extend deep-mutation technologies to enable measurement of many thousands of pairwise amino acid couplings in several homologs of a protein family – a deep coupling scan (DCS). The data show that cooperative interactions between residues are loaded in a sparse, evolutionarily conserved, spatially contiguous network of amino acids. The pattern of amino acid coupling is quantitatively captured in the coevolution of amino acid positions, especially as indicated by the statistical coupling analysis (SCA), providing experimental confirmation of the key tenets of this method. This work exposes the collective nature of physical constraints on protein function and clarifies its link with sequence analysis, enabling a general practical approach for understanding the structural basis for protein function.

scholarly journals Amino- and carboxy-terminal deletion mutants of Gs alpha are localized to the particulate fraction of transfected COS cells.

1992 ◽  
Vol 119 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Y S Juhnn ◽  
T L Jones ◽  
A M Spiegel
Keyword(s):  
Amino Acid ◽  
Particulate Fraction ◽  
Structural Basis ◽  
Similar Degree ◽  
Mutant Form ◽  
Amino Acid Residues ◽  
Wild Type ◽  
Amino Terminal ◽  
Gs Alpha ◽  
Mutant Forms

To elucidate the structural basis for membrane attachment of the alpha subunit of the stimulatory G protein (Gs alpha), mutant Gs alpha cDNAs with deletions of amino acid residues in the amino and/or carboxy termini were transiently expressed in COS-7 cells. The particulate and soluble fractions prepared from these cells were analyzed by immunoblot using peptide specific antibodies to monitor distribution of the expressed proteins. Transfection of mutant forms of Gs alpha with either 26 amino terminal residues deleted (delta 3-28) or with 59 amino terminal residues deleted (delta 1-59) resulted in immunoreactive proteins which localized primarily to the particulate fraction. Similarly, mutants with 10 (delta 385-394), 32 (delta 353-384), or 42 (delta 353-394) amino acid residues deleted from the carboxy terminus also localized to the particulate fraction, as did a mutant form of Gs alpha lacking amino acid residues at both the amino and carboxy termini (delta 3-28)/(delta 353-384). Mutant and wild type forms of Gs alpha demonstrated a similar degree of tightness in their binding to membranes as demonstrated by treatment with 2.5 M NaCl or 6 M urea, but some mutant forms were relatively resistant compared with wild type Gs alpha to solubilization by 15 mM NaOH or 1% sodium cholate. We conclude that: (a) deletion of significant portions of the amino and/or carboxyl terminus of Gs alpha is still compatible with protein expression; (b) deletion of these regions is insufficient to cause cytosolic localization of the expressed protein. The basis of Gs alpha membrane targeting remains to be elucidated.

scholarly journals Structural Basis for the Recognition of Isoleucyl-Adenylate and an Antibiotic, Mupirocin, by Isoleucyl-tRNA Synthetase

2001 ◽  
Vol 276 (50) ◽  
pp. 47387-47393 ◽  
Author(s):  
Takashi Nakama ◽  
Osamu Nureki ◽  
Shigeyuki Yokoyama
Keyword(s):  
Amino Acid ◽  
Thermus Thermophilus ◽  
High Energy ◽  
Trna Synthetase ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Trna Synthetases ◽  
Chemical Structures ◽  
Aminoacyl Trna Synthetases ◽  
The Common

An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the isoleucyl-tRNA synthetases (IleRSs) from the three primary kingdoms, whereas the antibiotic mupirocin inhibits only the eubacterial and archaeal IleRSs, but not the eukaryotic enzymes, and therefore is clinically used against methicillin-resistantStaphylococcus aureus. We determined the crystal structures of the IleRS from the thermophilic eubacterium,Thermus thermophilus, in complexes with Ile-AMS and mupirocin at 3.0- and 2.5-Å resolutions, respectively. A structural comparison of the IleRS·Ile-AMS complex with the adenylate complexes of other aminoacyl-tRNA synthetases revealed the common recognition mode of aminoacyl-adenylate by the class I aminoacyl-tRNA synthetases. The Ile-AMS and mupirocin, which have significantly different chemical structures, are recognized by many of the same amino acid residues of the IleRS, suggesting that the antibiotic inhibits the enzymatic activity by blocking the binding site of the high energy intermediate, Ile-AMP. In contrast, the two amino acid residues that concomitantly recognize Ile-AMS and mupirocin are different between the eubacterial/archaeal IleRSs and the eukaryotic IleRSs. Mutagenic analyses revealed that the replacement of the two residues significantly changed the sensitivity to mupirocin.

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