Probing the 2,4-Dichlorophenoxyacetate/α-Ketoglutarate Dioxygenase Substrate-Binding Site by Site-Directed Mutagenesis and Mechanism-Based Inactivation†

Biochemistry ◽  
2002 ◽  
Vol 41 (31) ◽  
pp. 9787-9794 ◽  
Author(s):  
Julie C. Dunning Hotopp ◽  
Robert P. Hausinger
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Substrate Binding Site ◽  
Ketoglutarate Dioxygenase

Identification of putative residues involved in the accessibility of the substrate-binding site of lipoxygenase by site-directed mutagenesis studies

2011 ◽  
Vol 509 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Cynthia Palmieri-Thiers ◽  
Jean-Christophe Alberti ◽  
Stéphane Canaan ◽  
Virginie Brunini ◽  
Claude Gambotti ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Substrate Binding Site

Site-directed mutagenesis of residues at the substrate binding-site of myeloperoxidase

1997 ◽  
Vol 67 (1-4) ◽  
pp. 85
Author(s):  
Ingeborg M. Kooter ◽  
Nicole Moguilevsky ◽  
Alex Bollen ◽  
Marianna Sijtsema ◽  
Kees Otto ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Substrate Binding Site

Analysis of the substrate-binding site of human carbonyl reductases CBR1 and CBR3 by site-directed mutagenesis

2009 ◽  
Vol 178 (1-3) ◽  
pp. 234-241 ◽  
Author(s):  
Yasser El-Hawari ◽  
Angelo D. Favia ◽  
Ewa S. Pilka ◽  
Michael Kisiela ◽  
Udo Oppermann ◽  
...  
Keyword(s):  
Binding Site ◽  
Substrate Binding ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Substrate Binding Site

Comprehensive in silico Study of GLUT10: Prediction of Possible Substrate Binding Sites and Interacting Molecules

2020 ◽  
Vol 21 (2) ◽  
pp. 117-130 ◽  
Author(s):  
Mohammad J. Hosen ◽  
Mahmudul Hasan ◽  
Sourav Chakraborty ◽  
Ruhshan A. Abir ◽  
Abdullah Zubaer ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Binding Site ◽  
Glucose Transporter ◽  
Substrate Binding ◽  
Mutation Screening ◽  
Homology Model ◽  
Connective Tissue Disorder ◽  
Crystallographic Structure ◽  
Substrate Binding Site

Objectives: The Arterial Tortuosity Syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and stenosis of the arteries with a propensity towards aneurysm formation and dissection. It is caused by mutations in the SLC2A10 gene that encodes the facilitative glucose transporter GLUT10. The molecules transported by and interacting with GLUT10 have still not been unambiguously identified. Hence, the study attempts to identify both the substrate binding site of GLUT10 and the molecules interacting with this site. Methods: As High-resolution X-ray crystallographic structure of GLUT10 was not available, 3D homology model of GLUT10 in open conformation was constructed. Further, molecular docking and bioinformatics investigation were employed. Results and Discussion: Blind docking of nine reported potential in vitro substrates with this 3D homology model revealed that substrate binding site is possibly made with PRO531, GLU507, GLU437, TRP432, ALA506, LEU519, LEU505, LEU433, GLN525, GLN510, LYS372, LYS373, SER520, SER124, SER533, SER504, SER436 amino acid residues. Virtual screening of all metabolites from the Human Serum Metabolome Database and muscle metabolites from Human Metabolite Database (HMDB) against the GLUT10 revealed possible substrates and interacting molecules for GLUT10, which were found to be involved directly or partially in ATS progression or different arterial disorders. Reported mutation screening revealed that a highly emergent point mutation (c. 1309G>A, p. Glu437Lys) is located in the predicted substrate binding site region. Conclusion: Virtual screening expands the possibility to explore more compounds that can interact with GLUT10 and may aid in understanding the mechanisms leading to ATS.

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