scholarly journals Deep Homology-Based Protein Contact-Map Prediction

2020 ◽  
Author(s):  
Omer Ronen ◽  
Or Zuk
Keyword(s):  
Fundamental Problem ◽  
Homology Modelling ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Physical Contact ◽  
Dimensional Structure ◽  
Evolutionary Information ◽  
Contact Map ◽  
Sequence Alignments ◽  
Three Dimensional Structure

AbstractPrediction of Proteins’ three dimensional structure and their contact maps from their amino-acid sequences is a fundamental problem in structural computational biology. The structure and contacts shed light on protein function, enhance our basic understanding of their molecular biology and may potentially aid in drug design. In recent years we have seen significant progress in protein contact map prediction from Multiple Sequence Alignments (MSA) of the target protein and its homologous, using signals of co-evolution and applying deep learning methods.Homology modelling is a popular and successful approach, where the structure of a protein is determined using information from known template structures of similar proteins, and has been shown to improve prediction even in cases of low sequence identity. Motivated by these observations, we developed Periscope, a method for homology-assisted contact map prediction using a deep convolutional network. Our method automatically integrates the co-evolutionary information from the MSA, and the physical contact information from the template structures.We apply our method to families of CAMEO and membrane proteins, and show improved prediction accuracy compared to the MSA-only based method RaptorX. Finally, we use our method to improve the subsequent task of predicting the proteins’ three dimensional structure based on the (improved) predicted contact map, and show initial promising results in this task too - our overall accuracy is comparable to the template-based Modeller software, yet the two methods are complementary and succeed on different targets.

PREDICTION OF THE THREE-DIMENSIONAL STRUCTURE OF THE ENZYMATIC PART OF T-PA

1987 ◽  
Author(s):  
A Heckel ◽  
K M Hasselbach
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Active Site ◽  
Serine Proteases ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Salt Bridges ◽  
Three Dimensional Structure ◽  
Insertions And Deletions

Up to now the three-dimensional structure of t-PA or parts of this enzyme is unknown. Using computer graphical methods the spatial structure of the enzymatic part of t-PA is predicted on the hypothesis, the three-dimensional backbone structure of t-PA being similar to that of other serine proteases. The t-PA model was built up in three steps:1) Alignment of the t-PA sequence with other serine proteases. Comparison of enzyme structures available from Brookhaven Protein Data Bank proved elastase as a basis for modeling.2) Exchange of amino acids of elastase differing from the t-PA sequence. The replacement of amino acids was performed such that backbone atoms overlapp completely and side chains superpose as far as possible.3) Modeling of insertions and deletions. To determine the spatial arrangement of insertions and deletions parts of related enzymes such as chymotrypsin or trypsin were used whenever possible. Otherwise additional amino acid sequences were folded to a B-turn at the surface of the proteine, where all insertions or deletions are located. Finally the side chain torsion angles of amino acids were optimised to prevent close contacts of neigh bouring atoms and to improve hydrogen bonds and salt bridges.The resulting model was used to explain binding of arginine 560 of plasminogen to the active site of t-PA. Arginine 560 interacts with Asp 189, Gly 19 3, Ser 19 5 and Ser 214 of t-PA (chymotrypsin numbering). Furthermore interaction of chromo-genic substrate S 2288 with the active site of t-PA was studied. The need for D-configuration of the hydrophobic amino acid at the N-terminus of this tripeptide derivative could be easily explained.

scholarly journals Unusual quaternary structure of a homodimeric synergistic-type toxin from mamba snake venom defines its molecular evolution

2020 ◽  
Vol 477 (20) ◽  
pp. 3951-3962
Author(s):  
Narumi Aoki-Shioi ◽  
Chacko Jobichen ◽  
J. Sivaraman ◽  
R. Manjunatha Kini
Keyword(s):  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Quaternary Structure ◽  
Hydrophobic Interactions ◽  
Biological Effects ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Common Structure

Snake venoms are complex mixtures of enzymes and nonenzymatic proteins that have evolved to immobilize and kill prey animals or deter predators. Among them, three-finger toxins (3FTxs) belong to the largest superfamily of nonenzymatic proteins. They share a common structure of three β-stranded loops extending like fingers from a central core containing all four conserved disulfide bonds. Most 3FTxs are monomers and through subtle changes in their amino acid sequences, they interact with different receptors, ion channels and enzymes to exhibit a wide variety of biological effects. The 3FTxs have further expanded their pharmacological space through covalent or noncovalent dimerization. Synergistic-type toxins (SynTxs) isolated from the deadly mamba venoms, although nontoxic, have been known to enhance the toxicity of other venom proteins. However, the details of three-dimensional structure and molecular mechanism of activity of this unusual class of 3FTxs are unclear. We determined the first three-dimensional structure of a SynTx isolated from Dendroaspis jamesoni jamesoni (Jameson's mamba) venom. The SynTx forms a unique homodimer that is held together by an interchain disulfide bond. The dimeric interface is elaborate and encompasses loops II and III. In addition to the inter-subunit disulfide bond, the hydrogen bonds and hydrophobic interactions between the monomers contribute to the dimer formation. Besides, two sulfate ions that mediate interactions between the monomers. This unique quaternary structure is evolved through noncovalent homodimers such as κ-bungarotoxins. This novel dimerization further enhances the diversity in structure and function of 3FTxs.

Characterization of RNase HII substrate recognition using RNase HII–argonaute chimaeric enzymes from Pyrococcus furiosus

2010 ◽  
Vol 426 (3) ◽  
pp. 337-344 ◽  
Author(s):  
Sayaka Kitamura ◽  
Kosuke Fujishima ◽  
Asako Sato ◽  
Daisuke Tsuchiya ◽  
Masaru Tomita ◽  
...  
Keyword(s):  
Amino Acid ◽  
Structural Model ◽  
Pyrococcus Furiosus ◽  
Three Dimensional ◽  
Rnase H ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
Piwi Domain ◽  
Three Dimensional Structure ◽  
Protein Secondary Structures

RNase H (ribonuclease H) is an endonuclease that cleaves the RNA strand of RNA–DNA duplexes. It has been reported that the three-dimensional structure of RNase H is similar to that of the PIWI domain of the Pyrococcus furiosus Ago (argonaute) protein, although the two enzymes share almost no similarity in their amino acid sequences. Eukaryotic Ago proteins are key components of the RNA-induced silencing complex and are involved in microRNA or siRNA (small interfering RNA) recognition. In contrast, prokaryotic Ago proteins show greater affinity for RNA–DNA hybrids than for RNA–RNA hybrids. Interestingly, we found that wild-type Pf-RNase HII (P. furiosus, RNase HII) digests RNA–RNA duplexes in the presence of Mn2+ ions. To characterize the substrate specificity of Pf-RNase HII, we aligned the amino acid sequences of Pf-RNase HII and Pf-Ago, based on their protein secondary structures. We found that one of the conserved secondary structural regions (the fourth β-sheet and the fifth α-helix of Pf-RNase HII) contains family-specific amino acid residues. Using a series of Pf-RNase HII–Pf-Ago chimaeric mutants of the region, we discovered that residues Asp110, Arg113 and Phe114 are responsible for the dsRNA (double-stranded RNA) digestion activity of Pf-RNase HII. On the basis of the reported three-dimensional structure of Ph-RNase HII from Pyrococcus horikoshii, we built a three-dimensional structural model of RNase HII complexed with its substrate, which suggests that these amino acids are located in the region that discriminates DNA from RNA in the non-substrate strand of the duplexes.

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 Structural Basis for Thermostability of β-Glycosidase from the Thermophilic Eubacterium Thermus nonproteolyticus HG102

2003 ◽  
Vol 185 (14) ◽  
pp. 4248-4255 ◽  
Author(s):  
Xinquan Wang ◽  
Xiangyuan He ◽  
Shoujun Yang ◽  
Xiaomin An ◽  
Wenrui Chang ◽  
...  
Keyword(s):  
Active Center ◽  
Three Dimensional ◽  
Structural Features ◽  
Dimensional Structure ◽  
Structural Basis ◽  
Glycosyl Hydrolases ◽  
Sequence Alignments ◽  
Three Dimensional Structure ◽  
The Core ◽  
Hyperthermophilic Enzymes

ABSTRACT The three-dimensional structure of a thermostable β-glycosidase (GlyTn) from the thermophilic eubacterium Thermus nonproteolyticus HG102 was determined at a resolution of 2.4 Å. The core of the structure adopts the (βα)8 barrel fold. The sequence alignments and the positions of the two Glu residues in the active center indicate that GlyTn belongs to the glycosyl hydrolases of retaining family 1. We have analyzed the structural features of GlyTn related to the thermostability and compared its structure with those of other mesophilic glycosidases from plants, eubacteria, and hyperthermophilic enzymes from archaea. Several possible features contributing to the thermostability of GlyTn were elucidated.

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