Superimpose: a 3D structural superposition server

Bauer, Raphael André; Bourne, Philip E.; Formella, Arno; Frömmel, Cornelius; Gille, Christoph; Goede, Andrean; Guerler, Aysam; Hoppe, Andreas; Knapp, Ernst‐Walter; Pöschel, Thorsten; Wittig, Burghardt; Ziegler, Valentin; Preißner, Robert

doi:10.1093/nar/gkn285

Cited by 32 publications

(25 citation statements)

References 38 publications

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“…[176] AURAmol Web service taking a candidate 2D or 3D molecular shape and using it to search for similarly shaped molecules in large databases. Provided by the University of York (http://www.cs.york.ac.uk/ auramol/index.html).…”

Section: Molegro Virtual Dockermentioning

confidence: 99%

Beware of docking!

Chen¹

2015

Trends in Pharmacological Sciences

486

340

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Section: Molegro Virtual Dockermentioning

confidence: 99%

Beware of docking!

Chen¹

2015

Trends in Pharmacological Sciences

486

340

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“…The P1 residues in API-A are highlighted by red stars. All figures of protein structure were produced with PyMOL (46), and the multialignment was generated based on the structural superposition (47).…”

mentioning

confidence: 99%

The Ternary Structure of the Double-headed Arrowhead Protease Inhibitor API-A Complexed with Two Trypsins Reveals a Novel Reactive Site Conformation

Bao

Zhou

Jiang

et al. 2009

Journal of Biological Chemistry

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The double-headed arrowhead protease inhibitors API-A and -B from the tubers of Sagittaria sagittifolia (Linn) feature two distinct reactive sites, unlike other members of their family. Although the two inhibitors have been extensively characterized, the identities of the two P1 residues in both API-A and -B remain controversial. The crystal structure of a ternary complex at 2.48 Å resolution revealed that the two trypsins bind on opposite sides of API-A and are 34 Å apart. The overall fold of API-A belongs to the ␤-trefoil fold and resembles that of the soybean Kunitz-type trypsin inhibitors. The two P1 residues were unambiguously assigned as Leu 87 and Lys 145 , and their identities were further confirmed by site-directed mutagenesis. Reactive site 1, composed of residues P5 Met 83 to P5 Ala 92 , adopts a novel conformation with the Leu 87 completely embedded in the S1 pocket even though it is an unfavorable P1 residue for trypsin. Reactive site 2, consisting of residues P5 Cys 141 to P5 Glu 150 , binds trypsin in the classic mode by employing a two-disulfide-bonded loop. Analysis of the two binding interfaces sheds light on atomic details of the inhibitor specificity and also promises potential improvements in enzyme activity by engineering of the reactive sites.Protease inhibitors (PIs) 4 are ubiquitously distributed in all organisms, including plants, animals, and microorganisms (1). They play vital roles in regulating their corresponding proteases, which are involved in many biological processes such as protein digestion, cell signal transmission, inflammation, apoptosis, blood coagulation, and embryogenesis (2). The clinical applications of PIs are widespread, and there is great interest in developing more potent therapeutic PIs for treating human diseases related to cancer (3), pancreatitis (4), thrombosis (5), and AIDS (6). To this end, the soybean Kunitz-type serine proteases inhibitors have been extensively studied (1,(7)(8)(9)(10)(11). The inhibitors of this family generally contain 170 -200 residues and have two disulfide bonds. Most members have only one reactive site located in the region of residues 60 -70 (7,10,(12)(13)(14). However, a few members possess two reactive sites that simultaneously bind two protease molecules and are thus termed double-headed inhibitors (15-18). All of these inhibitors are classified into family I3 of peptidase inhibitors (19). Most members are further grouped into subfamily I3A. However, the double-headed arrowhead PIs API-A and -B are grouped in subfamily I3B because of their very low sequence similarity to other members (19). In contrast to other double-headed PIs such as the Bowman-Birk and ovomucoid inhibitors, which have two identical reactive sites that have evolved by domain shuffling and gene duplication (1, 20 -25), both API-A and -B have two distinct reactive sites.API-A and -B were first purified from the tubers of Sagittaria sagittifolia (Linn) in 1979 (26). Both consist of 179 residues with three disulfide bonds and can inhibit a variety of serine pr...

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“…To determine the degree of secondary structure variability, the similarity measure was computed to compare the secondary structures of octapeptide sequences. The structures of probe and hit octapeptides were superposed to obtain the RMSD value using the Superimpose server 30. Also the percentage of occurrence of hydrophilic and hydrophobic residues was computed for the octapeptide sequence which adopts different secondary structure.…”

Section: Methodsmentioning

confidence: 99%

Search for identical octapeptides in unrelated proteins: Structural plasticity revisited

Saravanan

Selvaraj

2011

Biopolymers

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Since proteins are dynamic in nature, they can alter their local structure in response to changes in their environment factors such as temperature, pH, phosphorylation, and binding of other small molecules. These conformational changes are extremely important for the correct folding and functioning of proteins. There are also a number of diseases associated with protein conformational change such as amyloid diseases. To stimulate research into the above factors which specify one conformation over another, different theoretical models have been proposed and tested against sequence similar distant structure protein fragments. In order to simplify the computational complexity of identifying conformational changes in proteins, various local sequence search algorithms were employed and the structural plasticity in unrelated proteins was examined by various research groups. In the present work, we revisit the mechanism of structural plasticity in unrelated proteins with increased number of structures in Protein Data Bank by comparing identical octapeptides in unrelated proteins with dictionary of protein secondary structure extracted from existing experimental data. Our goal is to bring out the influence of hydrophobic residues, hydrophilic residues, flanking residues, difference in secondary structural propensities of surrounding residues, difference in phi-psi angles and local and nonlocal interactions in identical octapeptides adopting different conformations. Also we have used surrounding hydrophobicity, environment dependent interaction energy, atomic mean force potential, structural unit contacts and difference profiles models to explore the factors which cause structural plasticity. The results discussed here may provide insights into protein folding, design and function.

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Superimpose: a 3D structural superposition server

Cited by 32 publications

References 38 publications

Beware of docking!

Beware of docking!

The Ternary Structure of the Double-headed Arrowhead Protease Inhibitor API-A Complexed with Two Trypsins Reveals a Novel Reactive Site Conformation

Search for identical octapeptides in unrelated proteins: Structural plasticity revisited

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