Structural Diversity within the Mononuclear and Binuclear Active Sites ofN-Acetyl-d-glucosamine-6-phosphate Deacetylase†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (27) ◽  
pp. 7953-7962 ◽  
Author(s):  
Richard S. Hall ◽  
Shoshana Brown ◽  
Alexander A. Fedorov ◽  
Elena V. Fedorov ◽  
Chengfu Xu ◽  
...  
Keyword(s):  
Active Sites ◽  
Structural Diversity

scholarly journals In VivoImpact of Met221 Substitution in GOB Metallo-β-Lactamase

2012 ◽  
Vol 56 (4) ◽  
pp. 1769-1773 ◽  
Author(s):  
Jorgelina Morán-Barrio ◽  
María-Natalia Lisa ◽  
Alejandro J. Vila
Keyword(s):  
Antibiotic Resistance ◽  
Protein Stability ◽  
Metal Binding ◽  
Active Sites ◽  
Bacterial Resistance ◽  
Structural Diversity ◽  
Hydrophobic Core

ABSTRACTMetallo-β-lactamases (MβLs) represent one of the main mechanisms of bacterial resistance against β-lactam antibiotics. The elucidation of their mechanism has been limited mostly by the structural diversity among their active sites. All MβLs structurally characterized so far present a Cys or a Ser residue at position 221, which is critical for catalysis. GOB lactamases stand as an exception within this picture, possessing a Met residue in this location. We studied different mutants in this position, and we show that Met221 is essential for protein stability, most likely due to its involvement in a hydrophobic core. In contrast to other known MβLs, residue 221 is not involved in metal binding or in catalysis in GOB enzymes, further highlighting the structural diversity of MβLs. We also demonstrate the usefulness of protein periplasmic profiles to assess the contribution of protein stability to antibiotic resistance.

Conductive Metal and Covalent Organic Frameworks for Electrocatalysis: Design Principles, Recent Progress and Perspective

Nanoscale ◽  
2021 ◽  
Author(s):  
Jinyan Wang ◽  
Hongyin Hu ◽  
Shuanglong Lu ◽  
Jundie Hu ◽  
Han Zhu ◽  
...  
Keyword(s):  
Active Sites ◽  
Recent Progress ◽  
Structural Diversity ◽  
Design Principles ◽  
Covalent Organic Frameworks

Metal and covalent organic frameworks (MOFs/COFs) are emerging promising candidates in the field of catalysts due to their porous nature, chemically well-defined active sites and structural diversity. However, they are...

scholarly journals High-Resolution Crystal Structure of the Subclass B3 Metallo-β-Lactamase BJP-1: Rational Basis for Substrate Specificity and Interaction with Sulfonamides

2010 ◽  
Vol 54 (10) ◽  
pp. 4343-4351 ◽  
Author(s):  
Jean-Denis Docquier ◽  
Manuela Benvenuti ◽  
Vito Calderone ◽  
Magdalena Stoczko ◽  
Nicola Menciassi ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Bradyrhizobium Japonicum ◽  
Active Sites ◽  
Structural Diversity ◽  
Binding Pocket ◽  
Structural Basis ◽  
Side Chain ◽  
Functional Heterogeneity ◽  
Hydrophobic Binding

ABSTRACT Metallo-β-lactamases (MBLs) are important enzymatic factors in resistance to β-lactam antibiotics that show important structural and functional heterogeneity. BJP-1 is a subclass B3 MBL determinant produced by Bradyrhizobium japonicum that exhibits interesting properties. BJP-1, like CAU-1 of Caulobacter vibrioides, overall poorly recognizes β-lactam substrates and shows an unusual substrate profile compared to other MBLs. In order to understand the structural basis of these properties, the crystal structure of BJP-1 was obtained at 1.4-Å resolution. This revealed significant differences in the conformation and locations of the active-site loops, determining a rather narrow active site and the presence of a unique N-terminal helix bearing Phe-31, whose side chain binds in the active site and represents an obstacle for β-lactam substrate binding. In order to probe the potential of sulfonamides (known to inhibit various zinc-dependent enzymes) to bind in the active sites of MBLs, the structure of BJP-1 in complex with 4-nitrobenzenesulfonamide was also obtained (at 1.33-Å resolution), thereby revealing the mode of interaction of these molecules in MBLs. Interestingly, sulfonamide binding resulted in the displacement of the side chain of Phe-31 from its hydrophobic binding pocket, where the benzene ring of the molecule is now found. These data further highlight the structural diversity shown by MBLs but also provide interesting insights in the structure-function relationships of these enzymes. More importantly, we provided the first structural observation of MBL interaction with sulfonamides, which might represent an interesting scaffold for the design of MBL inhibitors.

scholarly journals Structural comparisons of host and African swine fever virus dUTPases reveal new clues for inhibitor development

2020 ◽  
pp. jbc.RA120.014005
Author(s):  
Rui Liang ◽  
Gang Wang ◽  
Ding Zhang ◽  
Gang Ye ◽  
Mengxia Li ◽  
...  
Keyword(s):  
Active Sites ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Structural Diversity ◽  
Fever Virus ◽  
Gene Encoding ◽  
Inhibitor Development ◽  
Ligand Free ◽  
The Difference ◽  
Swine Diseases

African swine fever, caused by the African swine fever virus (ASFV), is among the most significant swine diseases. There are currently no effective treatments against ASFV. ASFV contains a gene encoding a dUTPase (E165R), which is required for viral replication in swine macrophages, making it an attractive target for inhibitor development. However, the full structural details of the ASFV dUTPase and those of the comparable swine enzyme are not available, limiting further insights. Herein, we determine the crystal structures of ASFV dUTPase and swine dUTPase in both their ligand-free and ligand-bound forms. We observe that the swine enzyme employs a classical dUTPase architecture made up of three-subunit active sites, whereas the ASFV enzyme employs a novel two-subunit active site. We then performed a comparative analysis of all dUTPase structures uploaded in PDB, which showed classic and non-classical types were mainly determined by the C-terminal β-strand orientation, and the difference was mainly related to the four amino acids behind motif IV. Thus, our study not only explains the reason for the structural diversity of dUTPase but also reveals how to predict dUTPase type, which may have implications for the dUTPase family. Finally, we tested two dUTPase inhibitors developed for the Plasmodium falciparum dUTPase against the swine and ASFV enzymes. One of these compounds inhibited the ASFV dUTPase at low micromolar concentrations (Kd=15.6μM) and with some selectivity (~2x) over swine dUTPase. In conclusion, our study expands our understanding of the dUTPase family and may aid in the development of specific ASFV inhibitors.

Chemical and Structural Diversity in Cyclooxygenase Protein Active Sites

2005 ◽  
Vol 2 (11) ◽  
pp. 1533-1552 ◽  
Author(s):  
Ryan G. Huff ◽  
Ersin Bayram ◽  
Huan Tan ◽  
Stacy T. Knutson ◽  
Michael H. Knaggs ◽  
...  
Keyword(s):  
Active Sites ◽  
Structural Diversity ◽  
Protein Active Sites

scholarly journals Defect Engineering in Metal‒Organic Frameworks as Futuristic Options for Purification of Pollutants in an Aqueous Environment

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuhua Cao ◽  
Xin Mi ◽  
Xiang Li ◽  
Bo Wang
Keyword(s):  
Water Purification ◽  
Active Sites ◽  
High Surface ◽  
Metal Organic Frameworks ◽  
High Surface Area ◽  
Structural Diversity ◽  
Aqueous Environment ◽  
Defect Engineering ◽  
Geometric Framework ◽  
Metal Organic

Clean water scarcity is becoming an increasingly important worldwide issue. The water treatment industry is demanding the development of novel effective materials. Defect engineering in nanoparticles is among the most revolutionary of technologies. Because of their high surface area, structural diversity, and tailorable ability, Metal‒Organic Frameworks (MOFs) can be used for a variety of purposes including separation, storage, sensing, drug delivery, and many other issues. The application in wastewater treatment associated with water stable MOF‒based materials has been an emerging research topic in recent decades. Defect engineering is a sophisticated technique used to manufacture defects and to change the geometric framework of target compounds. Since MOFs have a series of designable structures and active sites, tailoring properties in MOFs by defect engineering is a novel concept. Defect engineering can excavate hidden active sites in MOFs, which can lead to better performance in many fields. Therefore, this technology will open new opportunities in water purification processes. However, there has been little effort to comprehensively discuss this topic. In this review, we provide an overview of the development of defect engineered MOFs for water purification processes. Furthermore, we discuss the potential applications of defect engineered materials.

scholarly journals Carbon Support Tuned Electrocatalytic Activity of Single-Site Metal-organic Framework toward Oxygen Reduction Reaction

2021 ◽  
Author(s):  
Wenjie Ma ◽  
Fei Wu ◽  
Ping Yu ◽  
Lanqun Mao
Keyword(s):  
Electrocatalytic Activity ◽  
Active Sites ◽  
Metal Organic Framework ◽  
Metal Organic Frameworks ◽  
Structural Diversity ◽  
Carbon Support ◽  
Reduction Reaction ◽  
Single Site ◽  
Metal Organic ◽  
Single Site Catalysts

Metal-organic frameworks (MOFs) possess fantastic features such as structural diversity, tunable accessible pores and atomically dispersed active sites, holding tremendous potentials as high versatile platforms for fabricating single-site catalysts. The...

What catalysis needs from the electron microscopist

1988 ◽  
Vol 46 ◽  
pp. 694-695
Author(s):  
Alexis T. Bell
Keyword(s):  
Active Sites ◽  
Heterogeneous Catalysts ◽  
Catalyst Deactivation ◽  
Surface Composition ◽  
Internal Surface ◽  
Active Phase ◽  
Atomic Scale ◽  
Metal Catalyst ◽  
Internal Surface Area ◽  
Porous Support

Heterogeneous catalysts, used in industry for the production of fuels and chemicals, are microporous solids characterized by a high internal surface area. The catalyticly active sites may occur at the surface of the bulk solid or of small crystallites deposited on a porous support. An example of the former case would be a zeolite, and of the latter, a supported metal catalyst. Since the activity and selectivity of a catalyst are known to be a function of surface composition and structure, it is highly desirable to characterize catalyst surfaces with atomic scale resolution. Where the active phase is dispersed on a support, it is also important to know the dispersion of the deposited phase, as well as its structural and compositional uniformity, the latter characteristics being particularly important in the case of multicomponent catalysts. Knowledge of the pore size and shape is also important, since these can influence the transport of reactants and products through a catalyst and the dynamics of catalyst deactivation.

Scanning luminescence x-ray microscopy: Progress toward selective staining using microspheres

1994 ◽  
Vol 52 ◽  
pp. 74-75
Author(s):  
C. Jacobsen ◽  
J. Fu ◽  
S. Mayer ◽  
Y. Wang ◽  
S. Williams
Keyword(s):  
Visible Light ◽  
Active Sites ◽  
Light Emission ◽  
Chinese Hamster ◽  
Polystyrene Spheres ◽  
Good Resistance ◽  
X Ray ◽  
Selective Staining ◽  
Visible Light Emission ◽  
Specific Labelling

In scanning luminescence x-ray microscopy (SLXM), a high resolution x-ray probe is used to excite visible light emission (see Figs. 1 and 2). The technique has been developed with a goal of localizing dye-tagged biochemically active sites and structures at 50 nm resolution in thick, hydrated biological specimens. Following our initial efforts, Moronne et al. have begun to develop probes based on biotinylated terbium; we report here our progress towards using microspheres for tagging.Our initial experiments with microspheres were based on commercially-available carboxyl latex spheres which emitted ~ 5 visible light photons per x-ray absorbed, and which showed good resistance to bleaching under x-ray irradiation. Other work (such as that by Guo et al.) has shown that such spheres can be used for a variety of specific labelling applications. Our first efforts have been aimed at labelling ƒ actin in Chinese hamster ovarian (CHO) cells. By using a detergent/fixative protocol to load spheres into cells with permeabilized membranes and preserved morphology, we have succeeded in using commercial dye-loaded, spreptavidin-coated 0.03μm polystyrene spheres linked to biotin phalloidon to label f actin (see Fig. 3).

The design and catalytic performance of molybdenum active sites on an MCM-41 framework for the aerobic oxidation of 5-hydroxymethylfurfural to 2,5-diformylfuran

2019 ◽  
Vol 9 (3) ◽  
pp. 811-821 ◽  
Author(s):  
Zhao-Meng Wang ◽  
Li-Juan Liu ◽  
Bo Xiang ◽  
Yue Wang ◽  
Ya-Jing Lyu ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Active Sites ◽  
Aerobic Oxidation ◽  
Catalytic Performance ◽  
Mcm 41

The catalytic activity decreases as –(SiO)3Mo(OH)(O) > –(SiO)2Mo(O)2 > –(O)4–MoO.

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