Crystal structures of SCP2-thiolases of Trypanosomatidae, human pathogens causing widespread tropical diseases: the importance for catalysis of the cysteine of the unique HDCF loop

2013 ◽  
Vol 455 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Rajesh K. Harijan ◽  
Tiila R. Kiema ◽  
Mikael P. Karjalainen ◽  
Neelanjana Janardan ◽  
M. R. N. Murthy ◽  
...  
Keyword(s):  
Reaction Mechanism ◽  
Crystal Structures ◽  
Biosynthetic Pathway ◽  
Tropical Diseases ◽  
Biosynthetic Enzyme ◽  
Human Pathogens ◽  
Unique Reaction ◽  
Trypanosomatid Parasites ◽  
Sterol Biosynthetic Pathway

Structural enzymological studies of trypanosomatid SCP2-thiolase reveal its unique reaction mechanism. These studies suggest that this enzyme is a biosynthetic enzyme, possibly involved in the sterol biosynthetic pathway, which is essential in the human pathogenic stages of some trypanosomatid parasites.

scholarly journals Visible-light photoexcitation of pyridine surface complex, leading to selective dehydrogenative cross-coupling with cyclohexane

2018 ◽  
Vol 20 (45) ◽  
pp. 28375-28381 ◽  
Author(s):  
Shimpei Naniwa ◽  
Akanksha Tyagi ◽  
Akira Yamamoto ◽  
Hisao Yoshida
Keyword(s):  
Reaction Mechanism ◽  
Visible Light ◽  
Cross Coupling ◽  
Surface Complex ◽  
Unique Reaction

A pyridine–TiO2 LMCT complex is excited by visible light to achieve selective DCC with cyclohexane via a unique reaction mechanism.

Crystal structures and snapshots along the reaction pathway of human phosphoserine phosphatase

2019 ◽  
Vol 75 (6) ◽  
pp. 592-604 ◽  
Author(s):  
Marie Haufroid ◽  
Manon Mirgaux ◽  
Laurence Leherte ◽  
Johan Wouters
Keyword(s):  
Molecular Dynamics ◽  
Reaction Mechanism ◽  
Crystal Structures ◽  
Reaction Pathway ◽  
Living Cells ◽  
Homocysteic Acid ◽  
Phosphoserine Phosphatase ◽  
Key Enzyme ◽  
The Subject ◽  
Dynamics Simulations

The equilibrium between phosphorylation and dephosphorylation is one of the most important processes that takes place in living cells. Human phosphoserine phosphatase (hPSP) is a key enzyme in the production of serine by the dephosphorylation of phospho-L-serine. It is directly involved in the biosynthesis of other important metabolites such as glycine and D-serine (a neuromodulator). hPSP is involved in the survival mechanism of cancer cells and has recently been found to be an essential biomarker. Here, three new high-resolution crystal structures of hPSP (1.5–2.0 Å) in complexes with phosphoserine and with serine, which are the substrate and the product of the reaction, respectively, and in complex with a noncleavable substrate analogue (homocysteic acid) are presented. New types of interactions take place between the enzyme and its ligands. Moreover, the loop involved in the open/closed state of the enzyme is fully refined in a totally unfolded conformation. This loop is further studied through molecular-dynamics simulations. Finally, all of these analyses allow a more complete reaction mechanism for this enzyme to be proposed which is consistent with previous publications on the subject.

scholarly journals Ubiquinone Biosynthesis over the Entire O2Range: Characterization of a Conserved O2-Independent Pathway

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Ludovic Pelosi ◽  
Chau-Duy-Tam Vo ◽  
Sophie Saphia Abby ◽  
Laurent Loiseau ◽  
Bérengère Rascalou ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Lipid Binding ◽  
The Novel ◽  
Human Pathogens ◽  
Terminal Electron Acceptor ◽  
Content Type ◽  
Metabolic Plasticity ◽  
Accessory Factor ◽  
Cellular Bioenergetics

ABSTRACTMost bacteria can generate ATP by respiratory metabolism, in which electrons are shuttled from reduced substrates to terminal electron acceptors, via quinone molecules like ubiquinone. Dioxygen (O2) is the terminal electron acceptor of aerobic respiration and serves as a co-substrate in the biosynthesis of ubiquinone. Here, we characterize a novel, O2-independent pathway for the biosynthesis of ubiquinone. This pathway relies on three proteins, UbiT (YhbT), UbiU (YhbU), and UbiV (YhbV). UbiT contains an SCP2 lipid-binding domain and is likely an accessory factor of the biosynthetic pathway, while UbiU and UbiV (UbiU-UbiV) are involved in hydroxylation reactions and represent a novel class of O2-independent hydroxylases. We demonstrate that UbiU-UbiV form a heterodimer, wherein each protein binds a 4Fe-4S cluster via conserved cysteines that are essential for activity. The UbiT, -U, and -V proteins are found in alpha-, beta-, and gammaproteobacterial clades, including several human pathogens, supporting the widespread distribution of a previously unrecognized capacity to synthesize ubiquinone in the absence of O2. Together, the O2-dependent and O2-independent ubiquinone biosynthesis pathways contribute to optimizing bacterial metabolism over the entire O2range.IMPORTANCEIn order to colonize environments with large O2gradients or fluctuating O2levels, bacteria have developed metabolic responses that remain incompletely understood. Such adaptations have been recently linked to antibiotic resistance, virulence, and the capacity to develop in complex ecosystems like the microbiota. Here, we identify a novel pathway for the biosynthesis of ubiquinone, a molecule with a key role in cellular bioenergetics. We link three uncharacterized genes ofEscherichia colito this pathway and show that the pathway functions independently from O2. In contrast, the long-described pathway for ubiquinone biosynthesis requires O2as a substrate. In fact, we find that many proteobacteria are equipped with the O2-dependent and O2-independent pathways, supporting that they are able to synthesize ubiquinone over the entire O2range. Overall, we propose that the novel O2-independent pathway is part of the metabolic plasticity developed by proteobacteria to face various environmental O2levels.

A special halide-stabilizing pair and enantioselectivity mechanism of DatA

2014 ◽  
Vol 70 (a1) ◽  
pp. C450-C450
Author(s):  
Lijun Guan ◽  
Hideya Yabuki ◽  
Masahiko Okai ◽  
Jun Ohtsuka ◽  
Masaru Tanokura
Keyword(s):  
Reaction Mechanism ◽  
Crystal Structures ◽  
Structural Information ◽  
Docking Simulation ◽  
Competitive Inhibitor ◽  
Residue Pair ◽  
Structural Basis ◽  
Chiral Compounds ◽  
In The Wild ◽  
Agrobacterium Tumefaciens C58

A novel haloalkane dehalogenase DatA from Agrobacterium tumefaciens C58 belongs to the HLD-II subfamily and hydrolyzes brominated and iodinated compounds, leading to the generation of the corresponding alcohol, a halide ion, and a proton. DatA possesses a unique Asn-Tyr residue pair instead of the Asn-Trp residue pair conserved among the subfamily members, thus the structural basis for its reaction mechanism merits elucidation. In addition, DatA is potentially useful for pharmaceutical and environmental applications, though several crystal structures of HLD-II dehalogenases have been reported so far, the determination of the DatA structure will provide an important contribution to those fields. This work provided insight into the reaction mechanism of DatA via a combination of X-ray crystallographic and computational analysis. The crystal structures of DatA and the Y109W mutant were determined at 1.70 Å [1] and 1.95 Å, respectively. The location of the active site was confirmed by using its novel competitive inhibitor, CHES. The structural information from these two crystal structures and the docking simulation with 1,3-dibromopropane revealed that the replacement of the Asn-Tyr pair with the Asn-Trp pair increases the binding affinity for 1,3-dibromopropane, due to the extra hydrogen bond between Trp109 and halogenated compounds; and that the key residue to bind halogenated substrate is only Asn43 in the wild-type DatA, while those in the Y109W mutant are the Asn-Trp pair. Furthermore, docking simulation using the crystal structures of DatA and some chiral compounds indicated that enantioselectivity of DatA toward brominated alkanes is determined by the large and small spaces around the halogen binding site.

scholarly journals Crystal Structures of Cytochrome P450 105P1 from Streptomyces avermitilis: Conformational Flexibility and Histidine Ligation State

2008 ◽  
Vol 191 (4) ◽  
pp. 1211-1219 ◽  
Author(s):  
Lian-Hua Xu ◽  
Shinya Fushinobu ◽  
Haruo Ikeda ◽  
Takayoshi Wakagi ◽  
Hirofumi Shoun
Keyword(s):  
Crystal Structures ◽  
Biosynthetic Pathway ◽  
Heme Iron ◽  
Streptomyces Avermitilis ◽  
Side Chain ◽  
Wild Type ◽  
Loop Region ◽  
Polyene Macrolide Antibiotic ◽  
Spectroscopic Characteristics ◽  
Ligand Free

ABSTRACT The polyene macrolide antibiotic filipin is widely used as a probe for cholesterol in biological membranes. The filipin biosynthetic pathway of Streptomyces avermitilis contains two position-specific hydroxylases, C26-specific CYP105P1 and C1′-specific CYP105D6. In this study, we describe the three X-ray crystal structures of CYP105P1: the ligand-free wild-type (WT-free), 4-phenylimidazole-bound wild-type (WT-4PI), and ligand-free H72A mutant (H72A-free) forms. The BC loop region in the WT-free structure has a unique feature; the side chain of His72 within this region is ligated to the heme iron. On the other hand, this region is highly disordered and widely open in WT-4PI and H72A-free structures, respectively. Histidine ligation of wild-type CYP105P1 was not detectable in solution, and a type II spectral change was clearly observed when 4-phenylimidazole was titrated. The H72A mutant showed spectroscopic characteristics that were almost identical to those of the wild-type protein. In the H72A-free structure, there is a large pocket that is of the same size as the filipin molecule. The highly flexible feature of the BC loop region of CYP105P1 may be required to accept a large hydrophobic substrate.

Unique reaction mechanism of preferential oxidation of CO over intermetallic Pt3Co catalysts: surface-OH-mediated formation of a bicarbonate intermediate

2016 ◽  
Vol 6 (6) ◽  
pp. 1642-1650 ◽  
Author(s):  
Shinya Furukawa ◽  
Kengo Ehara ◽  
Takayuki Komatsu
Keyword(s):  
Reaction Mechanism ◽  
Preferential Oxidation ◽  
Oxidation Of Co ◽  
Preferential Oxidation Of Co ◽  
Unique Reaction

A unique and novel reaction mechanism for the preferential oxidation of CO involving surface-OH-derived bicarbonate as an intermediate is reported.

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