scholarly journals X-ray crystal structure of the cytochrome P450 2B4 active site mutant F297A in complex with clopidogrel: Insights into compensatory rearrangements of the binding pocket

2013 ◽  
Vol 530 (2) ◽  
pp. 64-72 ◽  
Author(s):  
Manish B. Shah ◽  
Hyun-Hee Jang ◽  
Qinghai Zhang ◽  
C. David Stout ◽  
James R. Halpert
Keyword(s):  
Crystal Structure ◽  
Cytochrome P450 ◽  
Active Site ◽  
Binding Pocket ◽  
X Ray ◽  
Cytochrome P450 2B4

scholarly journals Crystal structure of a pyridoxal 5′-phosphate-dependent aspartate racemase derived from the bivalve mollusc Scapharca broughtonii

2017 ◽  
Vol 73 (12) ◽  
pp. 651-656 ◽  
Author(s):  
Taichi Mizobuchi ◽  
Risako Nonaka ◽  
Motoki Yoshimura ◽  
Katsumasa Abe ◽  
Shouji Takahashi ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Active Site ◽  
Metal Binding ◽  
Bivalve Mollusc ◽  
Active Site Residues ◽  
X Ray ◽  
Aspartate Racemase ◽  
Scapharca Broughtonii

Aspartate racemase (AspR) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that is responsible for D-aspartate biosynthesis in vivo. To the best of our knowledge, this is the first study to report an X-ray crystal structure of a PLP-dependent AspR, which was resolved at 1.90 Å resolution. The AspR derived from the bivalve mollusc Scapharca broughtonii (SbAspR) is a type II PLP-dependent enzyme that is similar to serine racemase (SR) in that SbAspR catalyzes both racemization and dehydration. Structural comparison of SbAspR and SR shows a similar arrangement of the active-site residues and nucleotide-binding site, but a different orientation of the metal-binding site. Superposition of the structures of SbAspR and of rat SR bound to the inhibitor malonate reveals that Arg140 recognizes the β-carboxyl group of the substrate aspartate in SbAspR. It is hypothesized that the aromatic proline interaction between the domains, which favours the closed form of SbAspR, influences the arrangement of Arg140 at the active site.

Difference in Conformation of Virginiamycin M1 in Chloroform and Bound Form in the 50S Ribosome or Streptogramin Acetyltransferase

2004 ◽  
Vol 57 (5) ◽  
pp. 415 ◽  
Author(s):  
Jason Dang ◽  
B. Mikael Bergdahl ◽  
Frances Separovic ◽  
Robert T. C. Brownlee ◽  
Robert P. Metzger
Keyword(s):  
Crystal Structure ◽  
High Resolution ◽  
Active Site ◽  
Major Change ◽  
X Ray ◽  
Binding Process ◽  
High Resolution Nmr ◽  
Virginiamycin M1

The conformation of virginiamycin M1 (VM1) in chloroform, determined by high-resolution NMR experiments, differs significantly from that of the X-ray crystal structure of VM1 bound to the 50S ribosome and to the active site of a streptogramin acetyltransferase enzyme. This implies that the binding process to these entities causes a major change in VM1 conformation.

Influence of the presence of the heme cofactor on the JK-loop structure in indoleamine 2,3-dioxygenase 1

2020 ◽  
Vol 76 (12) ◽  
pp. 1211-1221
Author(s):  
Manon Mirgaux ◽  
Laurence Leherte ◽  
Johan Wouters
Keyword(s):  
Crystal Structure ◽  
Cancer Research ◽  
Active Site ◽  
Loop Structure ◽  
X Ray Diffraction ◽  
Dynamic Information ◽  
X Ray ◽  
Indoleamine 2,3 Dioxygenase ◽  
First Time ◽  
Heme Cofactor

Indoleamine 2,3-dioxygenase 1 has sparked interest as an immunotherapeutic target in cancer research. Its structure includes a loop, named the JK-loop, that controls the orientation of the substrate or inhibitor within the active site. However, little has been reported about the crystal structure of this loop. In the present work, the conformation of the JK-loop is determined for the first time in the presence of the heme cofactor in the active site through X-ray diffraction experiments (2.44 Å resolution). Molecular-dynamics trajectories were also obtained to provide dynamic information about the loop according to the presence of cofactor. This new structural and dynamic information highlights the importance of the JK-loop in confining the labile heme cofactor to the active site.

scholarly journals The genome of a Bacteroidetes inhabitant of the human gut encodes a structurally distinct enoyl-acyl carrier protein reductase (FabI)

2020 ◽  
Vol 295 (22) ◽  
pp. 7635-7652
Author(s):  
Christopher D. Radka ◽  
Matthew W. Frank ◽  
Jiangwei Yao ◽  
Jayaraman Seetharaman ◽  
Darcie J. Miller ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Conformational Change ◽  
Conformational Changes ◽  
Active Site ◽  
Acyl Carrier Protein ◽  
Acid Synthesis ◽  
Binding Pocket ◽  
Structural Features ◽  
Antibacterial Drug ◽  
Carrier Protein

Enoyl-acyl carrier protein reductase (FabI) catalyzes a rate-controlling step in bacterial fatty-acid synthesis and is a target for antibacterial drug development. A phylogenetic analysis shows that FabIs fall into four divergent clades. Members of clades 1–3 have been structurally and biochemically characterized, but the fourth clade, found in members of phylum Bacteroidetes, is uncharacterized. Here, we identified the unique structure and conformational changes that distinguish clade 4 FabIs. Alistipes finegoldii is a prototypical Bacteroidetes inhabitant of the gut microbiome. We found that A. finegoldii FabI (AfFabI) displays cooperative kinetics and uses NADH as a cofactor, and its crystal structure at 1.72 Å resolution showed that it adopts a Rossmann fold as do other characterized FabIs. It also disclosed a carboxyl-terminal extension that forms a helix–helix interaction that links the protomers as a unique feature of AfFabI. An AfFabI·NADH crystal structure at 1.86 Å resolution revealed that this feature undergoes a large conformational change to participate in covering the NADH-binding pocket and establishing the water channels that connect the active site to the central water well. Progressive deletion of these interactions led to catalytically compromised proteins that fail to bind NADH. This unique conformational change imparted a distinct shape to the AfFabI active site that renders it refractory to a FabI drug that targets clade 1 and 3 pathogens. We conclude that the clade 4 FabI, found in the Bacteroidetes inhabitants of the gut, have several structural features and conformational transitions that distinguish them from other bacterial FabIs.

scholarly journals X-ray crystal structure of cytochrome P450 monooxygenase CYP101J2 fromSphingobium yanoikuyaestrain B2

2017 ◽  
Vol 85 (5) ◽  
pp. 945-950
Author(s):  
Birgit Unterweger ◽  
Nyssa Drinkwater ◽  
Priscilla Johanesen ◽  
Dena Lyras ◽  
Geoffrey J. Dumsday ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cytochrome P450 ◽  
Cytochrome P450 Monooxygenase ◽  
P450 Monooxygenase ◽  
X Ray
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