Structural basis of amino acid alpha helix propensity

Science ◽  
1993 ◽  
Vol 260 (5114) ◽  
pp. 1637-1640 ◽  
Author(s):  
M Blaber ◽  
X. Zhang ◽  
B. Matthews
Keyword(s):  
Amino Acid ◽  
Alpha Helix ◽  
Structural Basis ◽  
Helix Propensity

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 Efficient Conversion of Normal Prion Protein (PrP) by Abnormal Hamster PrP Is Determined by Homology at Amino Acid Residue 155

2001 ◽  
Vol 75 (10) ◽  
pp. 4673-4680 ◽  
Author(s):  
Suzette A. Priola ◽  
Joëlle Chabry ◽  
Kaman Chan
Keyword(s):  
Amino Acid ◽  
Prion Protein ◽  
Amino Acid Residue ◽  
Animal Species ◽  
Alpha Helix ◽  
Proteinase K ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
A Cell ◽  
Resistant Product

ABSTRACT In the transmissible spongiform encephalopathies, disease is closely associated with the conversion of the normal proteinase K-sensitive host prion protein (PrP-sen) to the abnormal proteinase K-resistant form (PrP-res). Amino acid sequence homology between PrP-res and PrP-sen is important in the formation of new PrP-res and thus in the efficient transmission of infectivity across species barriers. It was previously shown that the generation of mouse PrP-res was strongly influenced by homology between PrP-sen and PrP-res at amino acid residue 138, a residue located in a region of loop structure common to PrP molecules from many different species. In order to determine if homology at residue 138 also affected the formation of PrP-res in a different animal species, we assayed the ability of hamster PrP-res to convert a panel of recombinant PrP-sen molecules to protease-resistant PrP in a cell-free conversion system. Homology at amino acid residue 138 was not critical for the formation of protease-resistant hamster PrP. Rather, homology between PrP-sen and hamster PrP-res at amino acid residue 155 determined the efficiency of formation of a protease-resistant product induced by hamster PrP-res. Structurally, residue 155 resides in a turn at the end of the first alpha helix in hamster PrP-sen; this feature is not present in mouse PrP-sen. Thus, our data suggest that PrP-res molecules isolated from scrapie-infected brains of different animal species have different PrP-sen structural requirements for the efficient formation of protease-resistant PrP.

Structural Basis of Furan-Amino Acid Recognition by a Polyspecific Aminoacyl-tRNA-Synthetase and its Genetic Encoding in Human Cells

ChemBioChem ◽  
2014 ◽  
Vol 15 (12) ◽  
pp. 1755-1760 ◽  
Author(s):  
Moritz J. Schmidt ◽  
Annemarie Weber ◽  
Moritz Pott ◽  
Wolfram Welte ◽  
Daniel Summerer
Keyword(s):  
Amino Acid ◽  
Trna Synthetase ◽  
Human Cells ◽  
Structural Basis ◽  
Aminoacyl Trna Synthetase ◽  
Genetic Encoding ◽  
Amino Acid Recognition

scholarly journals Structural Basis for Human Norovirus Capsid Binding to Bile Acids

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Turgay Kilic ◽  
Anna Koromyslova ◽  
Grant S. Hansman
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Bile Acids ◽  
Natural Infection ◽  
Structural Basis ◽  
Amino Acid Side Chain ◽  
Blood Group Antigens ◽  
Human Norovirus ◽  
Bile Acid Binding ◽  
P Domain

ABSTRACT A recently developed human norovirus cell culture system revealed that the presence of bile enhanced or was an essential requirement for the growth of certain genotypes. Before this discovery, histo-blood group antigens (HBGAs) were the only well-studied cofactor known for human noroviruses, and there was evidence that several genotypes poorly bound HBGAs. Therefore, the purpose of this study was to investigate how human norovirus capsids interact with bile acids. We found that bile acids had low-micromolar affinities for GII.1, GII.10, and GII.19 capsids but did not bind GI.1, GII.3, GII.4, or GII.17. We showed that bile acid bound at a partially conserved pocket on the norovirus capsid-protruding (P) domain using X-ray crystallography. Amino acid sequence alignment and structural analysis delivered an explanation of selective bile acid binding. Intriguingly, we discovered that binding of the bile acid was the critical step to stabilize several P domain loops that optimally placed an essential amino acid side chain (Asp375) to bind HBGAs in an otherwise HBGA nonbinder (GII.1). Furthermore, bile acid enhanced HBGA binding for a known HBGA binder (GII.10). Altogether, these new data suggest that bile acid functions as a loop-stabilizing regulator and enhancer of HBGA binding for certain norovirus genotypes. IMPORTANCE Given that human norovirus virions likely interact with bile acid during a natural infection, our evidence that an HBGA nonbinder (GII.1) can be converted to an HBGA binder after bile acid binding is of major significance. Our data provide direct evidence that, like HBGAs, bile acid interaction on the capsid is an important cofactor for certain genotypes. However, more unanswered questions seem to arise from these new discoveries. For example, is there an association between the bile acid requirement and the prevalence of certain genotypes? That is, the GII.1 and GII.10 (bile acid binders) genotypes rarely caused outbreaks, whereas the GII.4 and GII.17 genotypes (bile acid nonbinders) were responsible for large epidemics. Therefore, it seems plausible that certain genotypes require bile acids, whereas others have modified their bile acid requirements on the capsid.

scholarly journals Do antibodies recognize amino acid side chains of protein antigens independently of the carbon backbone?

1988 ◽  
Vol 167 (6) ◽  
pp. 1841-1848 ◽  
Author(s):  
V H Van Cleave ◽  
C W Naeve ◽  
D W Metzger
Keyword(s):  
Amino Acid ◽  
Peptide Sequence ◽  
Structural Basis ◽  
Side Chains ◽  
Protein Antigens ◽  
Carbon Backbone ◽  
Internal Image ◽  
Amino Acid Side Chains ◽  
V Region ◽  
Complementarity Determining Region

In an effort to understand the structural basis for antigen mimicry by internal image antibodies, we determined the variable (V) region sequences of two mouse mAbs that mimic the rabbit Ig a1 allotype. The results showed that while the mAb light chains did not contain any allotype-related residues, both heavy chain V regions contained within complementarity-determining region 2 an unusual sequence homologous to the nominal antigen but in opposite orientation with respect to the carbon backbone. The ability of the internal image reversed sequence to express an a1-like determinant was tested directly by producing synthetic peptides that corresponded to the presumed antigenic regions of rabbit Ig and the mAb internal images, respectively. Although the two peptides presented the homologous residues in opposite orientations, they both completely inhibited at similar concentrations the binding of rabbit Ig to anti-a1 antibody. Conservative substitutions in the peptide sequence identified a paired Thr and Glu as being critical for expression of the a1 epitope. These findings indicate that antibodies can recognize the molecular environments created by amino acid side chains independently from the orientation of the protein carbon backbone.

scholarly journals Identification of amino acids essential for DNA binding and dimerization in p67SRF: implications for a novel DNA-binding motif

1993 ◽  
Vol 13 (1) ◽  
pp. 123-132
Author(s):  
A D Sharrocks ◽  
H Gille ◽  
P E Shaw
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Dna Binding ◽  
Transcriptional Activation ◽  
Serum Response Factor ◽  
Alpha Helix ◽  
Site Directed Mutagenesis ◽  
Binding Motif ◽  
Amino Acid Peptide ◽  
Serum Response

The serum response factor (p67SRF) binds to a palindromic sequence in the c-fos serum response element (SRE). A second protein, p62TCF binds in conjunction with p67SRF to form a ternary complex, and it is through this complex that growth factor-induced transcriptional activation of c-fos is thought to take place. A 90-amino-acid peptide, coreSRF, is capable for dimerizing, binding DNA, and recruiting p62TCF. By using extensive site-directed mutagenesis we have investigated the role of individual coreSRF amino acids in DNA binding. Mutant phenotypes were defined by gel retardation and cross-linking analyses. Our results have identified residues essential for either DNA binding or dimerization. Three essential basic amino acids whose conservative mutation severely reduced DNA binding were identified. Evidence which is consistent with these residues being on the face of a DNA binding alpha-helix is presented. A phenylalanine residue and a hexameric hydrophobic box are identified as essential for dimerization. The amino acid phasing is consistent with the dimerization interface being presented as a continuous region on a beta-strand. A putative second alpha-helix acts as a linker between these two regions. This study indicates that p67SRF is a member of a protein family which, in common with many DNA binding proteins, utilize an alpha-helix for DNA binding. However, this alpha-helix is contained within a novel domain structure.

scholarly journals Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins

2020 ◽  
Vol 117 (20) ◽  
pp. 10806-10817 ◽  
Author(s):  
Michael P. Torrens-Spence ◽  
Ying-Chih Chiang ◽  
Tyler Smith ◽  
Maria A. Vicent ◽  
Yi Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Convergent Evolution ◽  
Structural Features ◽  
Divergent Evolution ◽  
Structural Basis ◽  
Acid Decarboxylase ◽  
Substrate Selectivity ◽  
Amino Acid Decarboxylase ◽  
Catalytic Mechanisms

Radiation of the plant pyridoxal 5′-phosphate (PLP)-dependent aromatic l-amino acid decarboxylase (AAAD) family has yielded an array of paralogous enzymes exhibiting divergent substrate preferences and catalytic mechanisms. Plant AAADs catalyze either the decarboxylation or decarboxylation-dependent oxidative deamination of aromatic l-amino acids to produce aromatic monoamines or aromatic acetaldehydes, respectively. These compounds serve as key precursors for the biosynthesis of several important classes of plant natural products, including indole alkaloids, benzylisoquinoline alkaloids, hydroxycinnamic acid amides, phenylacetaldehyde-derived floral volatiles, and tyrosol derivatives. Here, we present the crystal structures of four functionally distinct plant AAAD paralogs. Through structural and functional analyses, we identify variable structural features of the substrate-binding pocket that underlie the divergent evolution of substrate selectivity toward indole, phenyl, or hydroxyphenyl amino acids in plant AAADs. Moreover, we describe two mechanistic classes of independently arising mutations in AAAD paralogs leading to the convergent evolution of the derived aldehyde synthase activity. Applying knowledge learned from this study, we successfully engineered a shortened benzylisoquinoline alkaloid pathway to produce (S)-norcoclaurine in yeast. This work highlights the pliability of the AAAD fold that allows change of substrate selectivity and access to alternative catalytic mechanisms with only a few mutations.

scholarly journals Two functionally distinct RNA-binding motifs in the regulatory domain of the protein kinase DAI.

1995 ◽  
Vol 15 (1) ◽  
pp. 358-364 ◽  
Author(s):  
S R Green ◽  
L Manche ◽  
M B Mathews
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Alpha Helix ◽  
Binding Domain ◽  
Single Amino Acid ◽  
Double Stranded Rna ◽  
C Terminus ◽  
Rna Binding Domain

The RNA-binding domain of the protein kinase DAI, the double-stranded RNA inhibitor of translation, contains two repeats of a motif that is also found in a number of other RNA-binding proteins. This motif consists of 67 amino acid residues and is predicted to contain a positively charged alpha helix at its C terminus. We have analyzed the effects of equivalent single amino acid changes in three conserved residues distributed over each copy of the motif. Mutants in the C-terminal portion of either repeat were severely defective, indicating that both copies of the motif are essential for RNA binding. Changes in the N-terminal and central parts of the motif were more debilitating if they were made in the first motif than in the second, suggesting that the first motif is the more important for RNA binding and that the second motif is structurally more flexible. When the second motif was replaced by a duplicate of the first motif, the ectopic copy retained its greater sensitivity to mutation, implying that the two motifs have distinct functions with respect to the process of RNA binding. Furthermore, the mutations have the same effect on the binding of double-stranded RNA and VA RNA, consistent with the existence of a single RNA-binding domain for both activating and inhibitory RNAs.

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