نتایج جستجو برای: binding pocket

تعداد نتایج: 429861  

2012
Yaw Sing Tan Paweł Śledź Steffen Lang Christopher J Stubbs David R Spring Chris Abell Robert B Best

The treatment of protein flexibility is a major challenge in structure-based drug design (SBDD) as proteins are dynamic and commonly undergo conformational changes to bind ligands. Consequently, binding sites may not be apparent in experimental structures of the unliganded protein. As a prototypical example, we focus here on the polo-box domain (PBD) of polo-like kinase 1 (Plk1), a serine/ thre...

Journal: :Journal of molecular biology 1995
A T Hadfield M A Oliveira K H Kim I Minor M J Kremer B A Heinz D Shepard D C Pevear R R Rueckert M G Rossmann

Structures have been determined of three human rhinovirus 14 (HRV14) compensation mutants that have resistance to the antiviral capsid binding compounds WIN 52035 and WIN 52084. In addition, the structure of HRV14 is reported, with a site-directed mutation at residue 1219 in VP1. A spontaneous mutation occurs at the same site in one of the compensation mutants. Some of the mutations are on the ...

Journal: :Proteins 2013
Daniel Demonte Eric J Drake Kok Hong Lim Andrew M Gulick Sheldon Park

We recently reported the engineering of monomeric streptavidin, mSA, corresponding to one subunit of wild type (wt) streptavidin tetramer. The monomer was designed by homology modeling, in which the streptavidin and rhizavidin sequences were combined to engineer a high affinity binding pocket containing residues from a single subunit only. Although mSA is stable and binds biotin with nanomolar ...

Journal: :Journal of immunology 2016
Jožica Vašl Alja Oblak Tina T Peternelj Javier Klett Sonsoles Martín-Santamaría Theresa L Gioannini Jerrold P Weiss Roman Jerala

Myeloid differentiation factor 2 (MD-2) is an extracellular protein, associated with the ectodomain of TLR4, that plays a critical role in the recognition of bacterial LPS. Despite high overall structural and functional similarity, human (h) and murine (m) MD-2 exhibit several species-related differences. hMD-2 is capable of binding LPS in the absence of TLR4, whereas mMD-2 supports LPS respons...

Journal: :The Journal of pharmacology and experimental therapeutics 2010
F Gbahou B Holst T W Schwartz

Epitopes determining the agonist property of two structurally distinct selective ligands for the human bombesin receptor subtype 3 (BB3), [D-Tyr6,(R)-Apa11,Phe13, Nle14]-bombesin(6-14) (Pep-1) and Ac-Phe-Trp-Ala-His(TauBzl)-Nip-Gly-Arg-NH2 (Pep-2), were mapped through systematic mutagenesis of the main ligand-binding pocket of the receptor. The mutational map for the smaller Pep-2 spanned the e...

Journal: :Proteins 2007
Takeshi Kawabata Nobuhiro Go

One of the simplest ways to predict ligand binding sites is to identify pocket-shaped regions on the protein surface. Many programs have already been proposed to identify these pocket regions. Examination of their algorithms revealed that a pocket intrinsically has two arbitrary properties, "size" and "depth". We proposed a new definition for pockets using two explicit adjustable parameters tha...

2017
Ling Li Hailong Zhang Man Zhang Mengxi Zhao Lijian Feng Xiao Luo Zhenting Gao Ying Huang Ophelia Ardayfio Ji-Hu Zhang Ying Lin Hong Fan Yuan Mi Guobin Li Lei Liu Leying Feng Fangjun Luo Lin Teng Wei Qi Johannes Ottl Andreas Lingel Dirksen E. Bussiere Zhengtian Yu Peter Atadja Chris Lu En Li Justin Gu Kehao Zhao

Polycomb repressive complex 2 (PRC2), a histone H3 lysine 27 methyltransferase, plays a key role in gene regulation and is a known epigenetics drug target for cancer therapy. The WD40 domain-containing protein EED is the regulatory subunit of PRC2. It binds to the tri-methylated lysine 27 of the histone H3 (H3K27me3), and through which stimulates the activity of PRC2 allosterically. Recently, w...

Journal: :EMBO reports 2009
Verena J Schuenemann Stephanie M Kralik Reinhard Albrecht Sukhdeep K Spall Kaye N Truscott David A Dougan Kornelius Zeth

In Escherichia coli, the ClpAP protease, together with the adaptor protein ClpS, is responsible for the degradation of proteins bearing an amino-terminal destabilizing amino acid (N-degron). Here, we determined the three-dimensional structures of ClpS in complex with three peptides, each having a different destabilizing residue--Leu, Phe or Trp--at its N terminus. All peptides, regardless of th...

2017
Natacha Cerisier Leslie Regad Dhoha Triki Anne-Claude Camproux Michel Petitjean

We analyzed 78 binding pockets of the human urokinase plasminogen activator (uPA) catalytic domain extracted from a data set of crystallized uPA-ligand complexes. These binding pockets were computed with an original geometric method that does NOT involve any arbitrary parameter, such as cutoff distances, angles, and so on. We measured the deviation from convexity of each pocket shape with the p...

2017
Serena Monaco Louise E Tailford Nathalie Juge Jesus Angulo

Saturation transfer difference (STD) NMR spectroscopy is extensively used to obtain epitope maps of ligands binding to protein receptors, thereby revealing structural details of the interaction, which is key to direct lead optimization efforts in drug discovery. However, it does not give information about the nature of the amino acids surrounding the ligand in the binding pocket. Herein, we rep...

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