Thermodynamic Analysis of a Hydrophobic Binding Site:  Probing the PDZ Domain with Nonproteinogenic Peptide Ligands

2004 ◽  
Vol 6 (20) ◽  
pp. 3429-3432 ◽  
Author(s):  
Dorina Saro ◽  
Edvin Klosi ◽  
Azrael Paredes ◽  
Mark R. Spaller
Keyword(s):  
Binding Site ◽  
Thermodynamic Analysis ◽  
Pdz Domain ◽  
Peptide Ligands ◽  
Hydrophobic Binding

Carbohydrate binding, quaternary structure and a novel hydrophobic binding site in two legume lectin oligomers from Dolichos biflorus 1 1Edited by R. Huber

1999 ◽  
Vol 286 (4) ◽  
pp. 1161-1177 ◽  
Author(s):  
Thomas W Hamelryck ◽  
Remy Loris ◽  
Julie Bouckaert ◽  
Minh-Hoa Dao-Thi ◽  
Gerard Strecker ◽  
...  
Keyword(s):  
Binding Site ◽  
Quaternary Structure ◽  
Carbohydrate Binding ◽  
Dolichos Biflorus ◽  
Legume Lectin ◽  
Hydrophobic Binding

Conformational changes in the third PDZ domain of the neuronal postsynaptic density protein 95

2019 ◽  
Vol 75 (4) ◽  
pp. 381-391 ◽  
Author(s):  
Ana Camara-Artigas ◽  
Javier Murciano-Calles ◽  
Jose C. Martínez
Keyword(s):  
Binding Site ◽  
Conformational Changes ◽  
Pdz Domain ◽  
Postsynaptic Density ◽  
Crystal Form ◽  
Space Groups ◽  
The Third ◽  
Conformational Plasticity ◽  
Α Helix ◽  
Postsynaptic Density Protein

PDZ domains are protein–protein recognition modules that interact with other proteins through short sequences at the carboxyl terminus. These domains are structurally characterized by a conserved fold composed of six β-strands and two α-helices. The third PDZ domain of the neuronal postsynaptic density protein 95 has an additional α-helix (α3), the role of which is not well known. In previous structures, a succinimide was identified in the β2–β3 loop instead of Asp332. The presence of this modified residue results in conformational changes in α3. In this work, crystallographic structures of the following have been solved: a truncated form of the third PDZ domain of the neuronal postsynaptic density protein 95 from which α3 has been removed, D332P and D332G variants of the protein, and a new crystal form of this domain showing the binding of Asp332 to the carboxylate-binding site of a symmetry-related molecule. Crystals of the wild type and variants were obtained in different space groups, which reflects the conformational plasticity of the domain. Indeed, the overall analysis of these structures suggests that the conformation of the β2–β3 loop is correlated with the fold acquired by α3. The alternate conformation of the β2–β3 loop affects the electrostatics of the carboxylate-binding site and might modulate the binding of different PDZ-binding motifs.

scholarly journals Localization of a Hydrophobic Binding Site for Anticoagulant Protein S on the β-Chain of Complement Regulator C4b-binding Protein

2000 ◽  
Vol 276 (6) ◽  
pp. 4330-4337 ◽  
Author(s):  
Joanna H. Webb ◽  
Bruno O. Villoutreix ◽  
Björn Dahlbäck ◽  
Anna M. Blom
Keyword(s):  
Binding Site ◽  
Binding Protein ◽  
Protein S ◽  
Hydrophobic Binding ◽  
Complement Regulator ◽  
Β Chain

scholarly journals Determination by photoaffinity labelling of the hydrophobic part of the binding site for acyl-CoA esters on acyl-CoA-binding protein from bovine liver

1990 ◽  
Vol 271 (1) ◽  
pp. 231-236 ◽  
Author(s):  
M Hach ◽  
S N Pedersen ◽  
T Börchers ◽  
P Højrup ◽  
J Knudsen
Keyword(s):  
Amino Acids ◽  
Staphylococcus Aureus ◽  
Binding Site ◽  
Binding Protein ◽  
Bovine Liver ◽  
Dodecanoic Acid ◽  
Reverse Phase ◽  
Hydrophobic Binding ◽  
The Difference ◽  
Peptide Maps

Acyl-CoA esters containing the photoreactive acids 12-(4′-azido-2′-nitrophenoxy)[1-14C]dodecanoic acid ([14C]AND-acid) or N-(4′-azido-2′-nitro-[3′-5′-3H]phenyl)-12-aminododecanoic acid ([3H]NANPA-acid) were synthesized. The photoreactive acyl-CoA esters could be bound to bovine acyl-CoA-binding protein (ACBP) and photocrosslinked to the protein. The photocrosslinked acyl-CoA-ACBP complex was separated from unlabelled ACBP on reverse-phase h.p.l.c. and the purified complex was digested with trypsin, Staphylococcus aureus V8 proteinase or endoproteinase Asp-N. By four independent peptide maps it was shown that the amino acids taking part in forming the hydrophobic binding site for acyl-CoA esters in bovine ACBP are located on the peptide segment from Asp21 to Asp38. Both photoreactive acyl-CoA esters used in this study labelled strongly in the segment from Tyr28 to Ala34. 12-(4′-Azido-2′-nitrophenoxy)[1-14C]-dodecanoyl-CoA ([14C]AND-CoA) also introduced a label at position Asp38, but o labelling was found before Ser29. In contrast, N-(4′-azido-2′-nitro[3′,5′-3H]phenyl)-12-aminododecanoyl-CoA [3H]NANPA-CoA) also labelled the segment from Asp21 to Tyr28. The difference in labelling by the two photoreactive ligands is most likely caused by different mobility of the arylazido group when linked to the fatty acid either through a phenolic O- or an anilinic N- bond.

Structure-based optimization of salt-bridge network across the complex interface of PTPN4 PDZ domain with its peptide ligands in neuroglioma

2017 ◽  
Vol 66 ◽  
pp. 63-68 ◽  
Author(s):  
Xian Xiao ◽  
Qiang-Hua He ◽  
Li-Yan Yu ◽  
Song-Qing Wang ◽  
Yang Li ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Salt Bridge ◽  
Peptide Ligands

scholarly journals Mapping of the ligand-binding site on the b′ domain of human PDI: interaction with peptide ligands and the x-linker region

2009 ◽  
Vol 423 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Lee J. Byrne ◽  
Ateesh Sidhu ◽  
A. Katrine Wallis ◽  
Lloyd W. Ruddock ◽  
Robert B. Freedman ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Disulfide Bonds ◽  
Substrate Binding ◽  
Peptide Ligands ◽  
Conformational Exchange ◽  
Secretory Proteins ◽  
Ligand Binding Site ◽  
Linker Region ◽  
Redox Active

PDI (protein disulfide-isomerase) catalyses the formation of native disulfide bonds of secretory proteins in the endoplasmic reticulum. PDI consists of four thioredoxin-like domains, of which two contain redox-active catalytic sites (a and a′), and two do not (b and b′). The b′ domain is primarily responsible for substrate binding, although the nature and specificity of the substrate-binding site is still poorly understood. In the present study, we show that the b′ domain of human PDI is in conformational exchange, but that its structure is stabilized by the addition of peptide ligands or by binding the x-linker region. The location of the ligand-binding site in b′ was mapped by NMR chemical shift perturbation and found to consist primarily of residues from the core β-sheet and α-helices 1 and 3. This site is where the x-linker region binds in the X-ray structure of b′x and we show that peptide ligands can compete with x binding at this site. The finding that x binds in the principal ligand-binding site of b′ further supports the hypothesis that x functions to gate access to this site and so modulates PDI activity.

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