Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The structure of endothiapepsin complexed with a Phe-Tyr reduced-bond inhibitor at 1.35?A resolution.

ABSTRACT: Endothiapepsin is a typical member of the aspartic proteinase family. The catalytic mechanism of this family is attributed to two conserved catalytic aspartate residues, which coordinate the hydrolysis of a peptide bond. An oligopeptide inhibitor (IC50 = 0.62?µM) based on a reduced-bond transition-state inhibitor of mucorpepsin was co-crystallized with endothiapepsin and the crystal structure of the enzyme-inhibitor complex was determined at 1.35?Å resolution. A total of 12 hydrogen bonds between the inhibitor and the active-site residues were identified. The resulting structure demonstrates a number of novel subsite interactions in the active-site cleft.

SUBMITTER: Guo J

PROVIDER: S-EPMC3943106 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The structure of endothiapepsin complexed with a Phe-Tyr reduced-bond inhibitor at 1.35 Å resolution.

Guo J J Cooper J B JB Wood S P SP

Acta crystallographica. Section F, Structural biology communications 20131224 Pt 1

Endothiapepsin is a typical member of the aspartic proteinase family. The catalytic mechanism of this family is attributed to two conserved catalytic aspartate residues, which coordinate the hydrolysis of a peptide bond. An oligopeptide inhibitor (IC50 = 0.62 µM) based on a reduced-bond transition-state inhibitor of mucorpepsin was co-crystallized with endothiapepsin and the crystal structure of the enzyme-inhibitor complex was determined at 1.35 Å resolution. A total of 12 hydrogen bonds betwee ...[more]

PMID: 24419612

Similar Datasets

Data of the subatomic resolution structure of glucose isomerase complexed with xylitol inhibitor.

Project description:Glucose isomerase (GI) is a crucial enzyme in industrial processes, including the production of high-fructose corn syrup, biofuels, and other renewable chemicals. Understanding the mechanisms of GI inhibition by GI inhibitors can offer valuable insights into enhancing production efficiency. We previously reported the subatomic resolution structure of Streptomyces rubiginosus GI (SruGI) complexed with a xylitol inhibitor, determined at 0.99 Å resolution, was reported. Structural analysis showed that the xylitol inhibitor is partially bound to the M1 binding site at the SruGI active site, enabling it to distinguish the xylitol-bound and -free state of SruGI. This structural information demonstrates that xylitol binding to the M1 site causes a conformational change in the metal binding site and the substrate binding channel of SruGI. Herein, detailed information on data collection and processing procedures of the subatomic resolution structure of the SruGI complexed with xylitol was reported.

| S-EPMC10792680 | biostudies-literature

Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 A resolution.

Project description:A high-resolution structure of a ligand-bound, soluble form of human monoglyceride lipase (MGL) is presented. The structure highlights a novel conformation of the regulatory lid-domain present in the lipase family as well as the binding mode of a pharmaceutically relevant reversible inhibitor. Analysis of the structure lacking the inhibitor indicates that the closed conformation can accommodate the native substrate 2-arachidonoyl glycerol. A model is proposed in which MGL undergoes conformational and electrostatic changes during the catalytic cycle ultimately resulting in its dissociation from the membrane upon completion of the cycle. In addition, the study outlines a successful approach to transform membrane associated proteins, which tend to aggregate upon purification, into a monomeric and soluble form.

| S-EPMC3081545 | biostudies-literature

Crystal structure of recombinant tyrosinase-binding protein MtaL at 1.35 A resolution.

Project description:Mushroom tyrosinase-associated lectin-like protein (MtaL) binds to mature Agaricus bisporus tyrosinase in vivo, but the exact physiological function of MtaL is unknown. In this study, the crystal structure of recombinant MtaL is reported at 1.35 Å resolution. Comparison of its structure with that of the truncated and cleaved MtaL present in the complex with tyrosinase directly isolated from mushroom shows that the general β-trefoil fold is conserved. However, differences are detected in the loop regions, particularly in the β2-β3 loop, which is intact and not cleaved in the recombinant MtaL. Furthermore, the N-terminal tail is rotated inwards, covering the tyrosinase-binding interface. Thus, MtaL must undergo conformational changes in order to bind mature mushroom tyrosinase. Very interestingly, the β-trefoil fold has been identified to be essential for carbohydrate interaction in other lectin-like proteins. Comparison of the structures of MtaL and a ricin-B-like lectin with a bound disaccharide shows that MtaL may have a similar carbohydrate-binding site that might be involved in glycoreceptor activity.

| S-EPMC4774885 | biostudies-literature

High-resolution structure of human carbonic anhydrase II complexed with acetazolamide reveals insights into inhibitor drug design.

Project description:The crystal structure of human carbonic anhydrase II (CA II) complexed with the inhibitor acetazolamide (AZM) has been determined at 1.1 A resolution and refined to an R(cryst) of 11.2% and an R(free) of 14.7%. As observed in previous CA II-inhibitor complexes, AZM binds directly to the zinc and makes several key interactions with active-site residues. The high-resolution data also showed a glycerol molecule adjacent to the AZM in the active site and two additional AZMs that are adventitiously bound on the surface of the enzyme. The co-binding of AZM and glycerol in the active site demonstrate that given an appropriate ring orientation and substituents, an isozyme-specific CA inhibitor may be developed.

| S-EPMC2765883 | biostudies-literature

Structure of tick anticoagulant peptide at 1.6 A resolution complexed with bovine pancreatic trypsin inhibitor.

Project description:The structure of tick anticoagulant peptide (TAP) has been determined by X-ray crystallography at 1.6 A resolution complexed with bovine pancreatic trypsin inhibitor (BPTI). The TAP-BPTI crystals are tetragonal, a = b = 46.87, c = 50.35 A, space group P41, four complexes per unit cell. The TAP molecules are highly dipolar and form an intermolecular helical array along the c-axis with a diameter of about 45 A. Individual TAP units interact in a head-to-tail fashion, the positive end of one molecule associating with the distal negative end of another, and vice versa. The BPTI molecules have a uniformly distributed positively charged surface that interacts extensively through 14 hydrogen bonds and two hydrogen bonded salt bridges with the helical groove around the helical TAP chains. Comparing the structure of TAP in TAP-BPTI with TAP bound to factor Xa(Xa) suggests a massive reorganization in the N-terminal tetrapeptide and the first disulfide loop of TAP (Cys5T-Cys15T) upon binding to Xa. The Tyr1(T)OH atom of TAP moves 14.2 A to interact with Asp189 of the S1 specificity site, Arg3(T)CZ moves 5.0 A with the guanidinium group forming a cation-pi-electron complex in the S4 subsite of Xa, while Lys7(T)NZ differs in position by 10.6 A in TAP-BPTI and TAP-Xa, all of which indicates a different pre-Xa-bound conformation for the N-terminal of TAP in its native state. In contrast to TAP, the BPTI structure of TAP-BPTI is practically the same as all those of previously determined structures of BPTI, only arginine and lysine side-chain conformations showing significant differences.

| S-EPMC2144540 | biostudies-other

Structure of a cupin protein Plu4264 from Photorhabdus luminescens subsp. laumondii TTO1 at 1.35 A resolution.

Project description:Proteins belonging to the cupin superfamily have a wide range of catalytic and noncatalytic functions. Cupin proteins commonly have the capacity to bind a metal ion with the metal frequently determining the function of the protein. We have been investigating the function of homologous cupin proteins that are conserved in more than 40 species of bacteria. To gain insights into the potential function of these proteins we have solved the structure of Plu4264 from Photorhabdus luminescens TTO1 at a resolution of 1.35 Å and identified manganese as the likely natural metal ligand of the protein.

| S-EPMC4300268 | biostudies-literature

Crystal structure of enhanced green fluorescent protein to 1.35 A resolution reveals alternative conformations for Glu222.

Project description:Enhanced Green Fluorescent Protein (EGFP) is one of the most widely used engineered variants of the original wild-type Green Fluorescent Protein. Here, we report the high resolution (1.35 Å) structure of EGFP crystallised in its untagged sequence form that reveals the combined impact of the F64L and S65T, that give rise to improved folding and spectral characteristics. The overall structure of EGFP is very similar to wt GFP, forming the classical β-barrel fold with the chromophore containing helix running through the core of the structure. Replacement of Phe64 with Leu in EGFP results in subtle rearrangement of hydrophobic core packing close to the chromophore including the reduction in surface exposure of two hydrophobic residues. Replacement of Ser65 with Thr has a significant impact on the local hydrogen bond network in the vicinity of the chromophore. Detailed analysis of electron density reveals that several residues close to the chromophore occupy at least two distinct conformations. This includes Glu222 that defines the charged state on the chromophore, with the two conformations having slightly different effects on the hydrogen bond network surrounding the chromophore. Hence, the reported high-resolution structure of EGFP has provided a long overdue molecular description of one of the most important fluorescent protein variants currently in general use.

| S-EPMC3473056 | biostudies-literature

N-terminal guanidinylation of TIPP (Tyr-Tic-Phe-Phe) peptides results in major changes of the opioid activity profile.

Project description:Derivatives of peptides of the TIPP (Tyr-Tic-Phe-Phe; Tic=1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) family containing a guanidino (Guan) function in place of the N-terminal amino group were synthesized in an effort to improve their blood-brain barrier permeability. Unexpectedly, N-terminal amidination significantly altered the in vitro opioid activity profiles. Guan-analogues of TIPP-related ? opioid antagonists showed ? partial agonist or mixed ? partial agonist/? partial agonist activity. Guanidinylation of the mixed ? agonist/? antagonists H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) and H-Dmt-Tic?[CH2NH]Phe-Phe-NH2 (DIPP-NH2[?]) converted them to mixed ? agonist/? agonists. A docking study revealed distinct positioning of DIPP-NH2 and Guan-DIPP-NH2 in the ? receptor binding site. Lys(3)-analogues of DIPP-NH2 and DIPP-NH2[?] (guanidinylated or non-guanidinylated) turned out to be mixed ?/? agonists with ? antagonist-, ? partial agonist- or ? full agonist activity. Compounds with some of the observed mixed opioid activity profiles have therapeutic potential as analgesics with reduced side effects or for treatment of cocaine addiction.

| S-EPMC3776131 | biostudies-literature

Crystal structure of AcrB complexed with linezolid at 3.5 A resolution.

Project description:AcrB is an inner membrane resistance-nodulation-cell division efflux pump and is part of the AcrAB-TolC tripartite efflux system. We have determined the crystal structure of AcrB with bound Linezolid at a resolution of 3.5 Å. The structure shows that Linezolid binds to the A385/F386 loops of the symmetric trimer of AcrB. A conformational change of a loop in the bottom of the periplasmic cleft is also observed.

| S-EPMC3679416 | biostudies-literature

Structure of cyanobacterial photosystem I complexed with ferredoxin at 1.97 A resolution.

Project description:Photosystem I (PSI) is a light driven electron pump transferring electrons from Cytochrome c6 (Cyt c6) to Ferredoxin (Fd). An understanding of this electron transfer process is hampered by a paucity of structural detail concerning PSI:Fd interface and the possible binding sites of Cyt c6. Here we describe the high resolution cryo-EM structure of Thermosynechococcus elongatus BP-1 PSI in complex with Fd and a loosely bound Cyt c6. Side chain interactions at the PSI:Fd interface including bridging water molecules are visualized in detail. The structure explains the properties of mutants of PsaE and PsaC that affect kinetics of Fd binding and suggests a molecular switch for the dissociation of Fd upon reduction. Calorimetry-based thermodynamic analyses confirms a single binding site for Fd and demonstrates that PSI:Fd complexation is purely driven by entropy. A possible reaction cycle for the efficient transfer of electrons from Cyt c6 to Fd via PSI is proposed.

| S-EPMC9467995 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data