Complexed and ligand-free high-resolution structures of urate oxidase (Uox) fromAspergillus flavus: a reassignment of the active-site binding mode

2004 ◽  
Vol 60 (3) ◽  
pp. 453-462 ◽  
Author(s):  
Pascal Retailleau ◽  
Nathalie Colloc'h ◽  
Denis Vivarès ◽  
Françoise Bonneté ◽  
Bertrand Castro ◽  
...  
Keyword(s):  
High Resolution ◽  
Active Site ◽  
Binding Mode ◽  
Urate Oxidase ◽  
Ligand Free ◽  
Site Binding

Protein modeling and active site binding mode interactions of myrosinase–sinigrin in Brassica juncea—An in silico approach

2011 ◽  
Vol 29 (5) ◽  
pp. 740-746 ◽  
Author(s):  
Rajender Kumar ◽  
Sandeep Kumar ◽  
Seema Sangwan ◽  
Inderjit Singh Yadav ◽  
Rakesh Yadav
Keyword(s):  
Brassica Juncea ◽  
Active Site ◽  
In Silico ◽  
Binding Mode ◽  
Protein Modeling ◽  
Mode Interactions ◽  
Site Binding

Identification of quasi-stable water molecules near the Thr73–Lys13 catalytic diad of Bacillus sp. TB-90 urate oxidase by X-ray crystallography with controlled humidity

2020 ◽  
Author(s):  
Takao Hibi ◽  
Takafumi Itoh
Keyword(s):  
Active Site ◽  
Essential Role ◽  
Profile Analysis ◽  
Binding Mode ◽  
Site Directed Mutagenesis ◽  
Urate Oxidase ◽  
Water Molecules ◽  
Bacillus Sp ◽  
Water Network ◽  
Ph Profile

Abstract Urate oxidases (UOs) catalyze the cofactor-independent oxidation of uric acid, and an extensive water network in the active site has been suggested to play an essential role in the catalysis. For our present analysis of the structure and function of the water network, the crystal qualities of Bacillus sp. TB-90 urate oxidase were improved by controlled dehydration using the humid air and glue-coating method. After the dehydration, the P21212 crystals were transformed into the I222 space group, leading to an extension of the maximum resolution to 1.42 Å. The dehydration of the crystals revealed a significant change in the five-water-molecules’ binding mode in the vicinity of the catalytic diad, indicating that these molecules are quasi-stable. The pH profile analysis of log(kcat) gave two pKa values: pKa1 at 6.07 ± 0.07 and pKa2 at 7.98 ± 0.13. The site-directed mutagenesis of K13, T73 and N276 involved in the formation of the active-site water network revealed that the activities of these mutant variants were significantly reduced. These structural and kinetic data suggest that the five quasi-stable water molecules play an essential role in the catalysis of the cofactor-independent urate oxidation by reducing the energy penalty for the substrate-binding or an on–off switching for the proton-relay rectification.

(R)-3-Amidinophenylalanine-Derived Inhibitors of Factor Xa with a Novel Active-Site Binding Mode

2002 ◽  
Vol 383 (7-8) ◽  
Author(s):  
M. M. Mueller ◽  
S. Sperl ◽  
J. Stürzebecher ◽  
W. Bode ◽  
L. Moroder
Keyword(s):  
Active Site ◽  
Factor Xa ◽  
Binding Mode ◽  
Site Binding

Recent insights into lytic polysaccharide monooxygenases (LPMOs)

2018 ◽  
Vol 46 (6) ◽  
pp. 1431-1447 ◽  
Author(s):  
Tobias Tandrup ◽  
Kristian E. H. Frandsen ◽  
Katja S. Johansen ◽  
Jean-Guy Berrin ◽  
Leila Lo Leggio
Keyword(s):  
Active Site ◽  
Room Temperature ◽  
Experimental Studies ◽  
Binding Mode ◽  
Structural Features ◽  
Oxygen Species ◽  
Animal Kingdom ◽  
X Ray ◽  
Lytic Polysaccharide Monooxygenases ◽  
Polysaccharide Monooxygenases

Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes discovered within the last 10 years. By degrading recalcitrant substrates oxidatively, these enzymes are major contributors to the recycling of carbon in nature and are being used in the biorefinery industry. Recently, two new families of LPMOs have been defined and structurally characterized, AA14 and AA15, sharing many of previously found structural features. However, unlike most LPMOs to date, AA14 degrades xylan in the context of complex substrates, while AA15 is particularly interesting because they expand the presence of LPMOs from the predominantly microbial to the animal kingdom. The first two neutron crystallography structures have been determined, which, together with high-resolution room temperature X-ray structures, have putatively identified oxygen species at or near the active site of LPMOs. Many recent computational and experimental studies have also investigated the mechanism of action and substrate-binding mode of LPMOs. Perhaps, the most significant recent advance is the increasing structural and biochemical evidence, suggesting that LPMOs follow different mechanistic pathways with different substrates, co-substrates and reductants, by behaving as monooxygenases or peroxygenases with molecular oxygen or hydrogen peroxide as a co-substrate, respectively.

scholarly journals Crystal structures of DNA polymerase I capture novel intermediates in the DNA synthesis pathway

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nicholas Chim ◽  
Lynnette N Jackson ◽  
Anh M Trinh ◽  
John C Chaput
Keyword(s):  
High Resolution ◽  
Dna Synthesis ◽  
Crystal Structures ◽  
Dna Polymerase ◽  
Active Site ◽  
Dna Polymerase I ◽  
Dynamic Nature ◽  
Enzyme Active Site ◽  
Polymerase I ◽  
In Cells

High resolution crystal structures of DNA polymerase intermediates are needed to study the mechanism of DNA synthesis in cells. Here we report five crystal structures of DNA polymerase I that capture new conformations for the polymerase translocation and nucleotide pre-insertion steps in the DNA synthesis pathway. We suggest that these new structures, along with previously solved structures, highlight the dynamic nature of the finger subdomain in the enzyme active site.

scholarly journals High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form

2018 ◽  
Vol 74 (11) ◽  
pp. 717-724 ◽  
Author(s):  
Shukun Luo ◽  
Ke Xu ◽  
Shaoyun Xiang ◽  
Jie Chen ◽  
Chunyun Chen ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Resolution ◽  
Crystal Structures ◽  
Active Site ◽  
Crystal Form ◽  
Crystal Forms ◽  
Cellular Processes ◽  
Potential Target ◽  
Indoleamine 2,3 Dioxygenase

Human indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-dependent enzyme with important roles in many cellular processes and is a potential target for drug discovery against cancer and other diseases. Crystal structures of IDO1 in complex with various inhibitors have been reported. Many of these crystals belong to the same crystal form and most of the reported structures have resolutions in the range 3.2–2.3 Å. Here, three new crystal forms of human IDO1 obtained by introducing a surface mutation, K116A/K117A, distant from the active site are reported. One of these crystal forms diffracted to 1.5 Å resolution and can be readily used for soaking experiments to determine high-resolution structures of IDO1 in complex with the substrate tryptophan or inhibitors that coordinate the heme. In addition, this mutant was used to produce crystals of a complex with an inhibitor that targets the apo form of the enzyme under the same conditions; the structure of this complex was determined at 1.7 Å resolution. Overall, this mutant represents a robust platform for determining the structures of inhibitor and substrate complexes of IDO1 at high resolution.

Sign in / Sign up

Export Citation Format

Share Document