Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play important roles in protein catabolism, antigen processing, degenerative diseases, and breast cancer progression. Determination of the crystal structures cathepsin complex with pepstatin at 2.5 A resolution provides insights into inhibitor binding targeting for this two-chain, N-glycosylated aspartic protease. Comparison bound rhizopuspepsin human renin-inhibitor revealed differences subsite inhibitor-enzyme interactions that...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfluence of stereochemistry on activity and binding modes for C2 symmetry-based diol inhibitors HIV-1 proteaseMadhusoodan V. Hosur, T. Narayana Bhat, Dale J. Kempf, Eric Baldwin, Beishan Liu, Sergei Gulnik, Norman E. Wideburg, Daniel W. Norbeck, Krzysztof Appelt, John EricksonCite this: Am. Chem. Soc. 1994, 116, 3, 847–855Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February...

Abstract We report the first atomic resolution structure of an insect virus determined by single crystal X‐ray diffraction. Black beetle has a bipartite RNA genome encapsulated in particle. The capsid contains 180 protomers arranged on T = 3 surface lattice. quaternary organization is similar to that observed plant structures. consist basic, crystallographically disordered amino terminus (64 residues), β‐barrel as seen other animal and subunits, outer protrusion composed predominantly...

The protein crystallography beamline (PX-BL21), installed at the 1.5 T bending-magnet port Indian synchrotron (Indus-2), is now available to users. can be used for X-ray diffraction measurements on a single crystal of macromolecules such as proteins, nucleic acids and their complexes. PX-BL21 has working energy range 5-20 keV accessing absorption edges heavy elements commonly phasing. A double-crystal monochromator [Si(111) Si(220)] pair rhodium-coated mirrors are beam monochromatization...

Proteins can be unfolded in a regulated way by use of different strategies, which include changes temperature or pressure, addition chemical denaturants to and/or alteration the pH value solution protein is immersed. It would interest know if onset unfolding these methods has common starting point, since misfolding that preceded associated with number neurological diseases. We have used technique X-ray crystallography identify hen egg white lysozyme (HEWL), relatively small two-domain enzyme...

Structural snapshots of each step in the catalytic cycle would help development inhibitors human immunodeficiency virus type 1 protease (HIV-1 PR) as effective drugs against HIV/AIDS. We report here one snapshot obtained by determining structure enzyme-substrate complex under conditions where activity enzyme is greatly reduced. The 1.76 A crystal shows oligopeptide substrate, AETFYVDGAA, converted situ into a gem-diol tetrahedral intermediate (TI). neutral and hydroxyl oxygens forms very...

Three-dimensional structure of an asymmetrically mutated (C95M) tethered human immunodeficiency virus type 1 protease enzyme (HIV-1 PR) has been determined in unliganded form using X-ray diffraction data to 1.9 Å resolution. The structure, refined X-PLOR R factor 19.5%, is unexpectedly similar the ligand-bound native enzyme, rather than ligand-free enzyme. In particular, two flaps dimer are a closed configuration. environments around M95 and C1095 identical, showing no structural effect this...

Hydrogen bonding interactions are one of the most important chemical among materials, especially biological which help confer specificity, is crucial for their efficient functioning. Recently, low-barrier hydrogen bonds (LBHBs) have been proposed to play a critical role in enzyme catalysis. In this review, tools identify LBHBs described, along with analyses neutron crystal structures small molecules geometric parameters characteristic LBHBs, assumed be characterized by dynamic disorder bond...

HIV-1 protease is an effective target for designing drugs against AIDS, and structural information about the true transition state correct mechanism can provide important inputs. We present here three-dimensional structure of a bi-product complex between two cleavage product peptides AETF YVDGAA. The structure, refined synchrotron data to 1.65 Å resolution, shows occurrence reaction in crystal, with still held enzyme active site. separation scissile carbon nitrogen atoms 2.67 Å, which...

Familial inheritance of breast and ovarian cancer is attributed to mutations discovered in functional domains BRCA1 gene. a multifunctional protein responsible for maintaining the genomic integrity has transcriptional regulatory function encoded its C-terminal region. The different amino-terminal e extensions BRCT domain are transcription activation. However, only (1649–1859) amino acids have been explored structural characteristics. Noting importance extended region N-terminus regions which...

HIV-1 protease is an effective target for the design of drugs against AIDS. To help this process drug design, three-dimensional structures have been determined complexes between and a variety transition-state analogue inhibitors. The true transition state, however, has not structurally characterized. crystal structure C95M/C1095A tethered dimer shows distinctive feature in which two flaps enzyme are ‘closed conformation’ even unliganded state. This unique utilized here to study complexed...

The alkaline phosphatase (AP) is a bi-metalloenzyme of potential applications in biotechnology and bioremediation, which phosphate monoesters are nonspecifically hydrolysed under conditions to yield inorganic phosphate. hydrolysis occurs through an enzyme intermediate the catalytic residue phosphorylated. reaction, also requires third metal ion, proposed proceed mechanism in-line displacement involving trigonal bipyramidal transition state. Stabilizing state by bidentate hydrogen bonding has...

Abstract Temporal binding of urea to lysozyme was examined using X-ray diffraction single crystals urea/lysozyme complexes prepared by soaking native in solutions containing 9 M urea. Four different soak times 2, 4, 7 and 10 hours were used. The five crystal structures (including the lysozyme), refined 1.6 Å resolution, reveal that as time increased, more first-shell water molecules are replaced number hydrogen bonds between protein is similar However, van der Waals contacts from almost...

Saporin is a single chain ribosome‐inactivating protein produced by the plant Saponaria officinalis . Several isoforms of saporin have been isolated from various parts plant. In present study recombinant 5 and 6 were in Escherichia coli Saporin‐6 was found to be more active than saporin‐5 its N‐glycosidase, cytotoxic, genomic DNA fragmentation activities. Earlier, has shown bind low‐density lipoprotein receptor‐related (LRP), however, this sensitivities LRP‐negative LRP‐positive cell lines...

The eukaryotic 60S-ribosomal stalk is composed of acidic ribosomal proteins (P1 and P2) neutral protein P0, which are thought to be associated as a pentameric structure, [2P1, 2P2, P0]. Plasmodium falciparum P2 (PfP2) appears play additional non-ribosomal functions with its tendency for homo-oligomerization. Recombinant bacterially expressed PfP2 also undergoes self-association, shown by SDS-PAGE analysis light scattering studies. Secondary structure prediction algorithms predict the native...

Even though more than 200 three‐dimensional structures of HIV‐1 protease complexed to a variety inhibitors are available in the Protein Data Bank; very few unliganded protein have been determined. We recently solved tethered dimer mutants resolutions 1.9 Å and 2.1 Å, found that flaps assume closed‐flap conformation even absence any bound ligand. report comparison structure with inhibitor complexes view accurately identifying structural changes ligand can induce on binding crystal. These...