Two Distinct Substrate Binding Modes for the Normal and Reverse Prenylation of Hapalindoles by the Prenyltransferase AmbP3

2017 ◽  
Vol 57 (2) ◽  
pp. 560-563 ◽  
Author(s):  
Chin Piow Wong ◽  
Takayoshi Awakawa ◽  
Yu Nakashima ◽  
Takahiro Mori ◽  
Qin Zhu ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Binding Modes

scholarly journals Determination of tyrosinase substrate-binding modes reveals mechanistic differences between type-3 copper proteins

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Mor Goldfeder ◽  
Margarita Kanteev ◽  
Sivan Isaschar-Ovdat ◽  
Noam Adir ◽  
Ayelet Fishman
Keyword(s):  
Substrate Binding ◽  
Copper Proteins ◽  
Binding Modes ◽  
Type 3

scholarly journals Substrate Recognition by AAA+ ATPases: Distinct Substrate Binding Modes in ATP-Dependent Protease Yme1 of the Mitochondrial Intermembrane Space

2007 ◽  
Vol 27 (7) ◽  
pp. 2476-2485 ◽  
Author(s):  
Martin Graef ◽  
Georgeta Seewald ◽  
Thomas Langer
Keyword(s):  
Molecular Mechanisms ◽  
Substrate Binding ◽  
Substrate Recognition ◽  
Intermembrane Space ◽  
Binding Modes ◽  
General Role ◽  
Mitochondrial Inner Membrane ◽  
Assembly Factor ◽  
Substrate Binding Sites ◽  
Energy Dependent

ABSTRACT The energy-dependent proteolysis of cellular proteins is mediated by conserved proteolytic AAA+ complexes. Two such machines, the m- and i-AAA proteases, are present in the mitochondrial inner membrane. They exert chaperone-like properties and specifically degrade nonnative membrane proteins. However, molecular mechanisms of substrate engagement by AAA proteases remained elusive. Here, we define initial steps of substrate recognition and identify two distinct substrate binding sites in the i-AAA protease subunit Yme1. Misfolded polypeptides are recognized by conserved helices in proteolytic and AAA domains. Structural modeling reveals a lattice-like arrangement of these helices at the surface of hexameric AAA protease ring complexes. While helices within the AAA domain apparently play a general role for substrate binding, the requirement for binding to surface-exposed helices within the proteolytic domain is determined by the folding and membrane association of substrates. Moreover, an assembly factor of cytochrome c oxidase, Cox20, serves as a substrate-specific cofactor during proteolysis and modulates the initial interaction of nonassembled Cox2 with the protease. Our findings therefore reveal the existence of alternative substrate recognition pathways within AAA proteases and shed new light on molecular mechanisms ensuring the specificity of proteolysis by energy-dependent proteases.

Identification of FDA Approved Drugs Targeting COVID-19 Virus by Structure-Based Drug Repositioning (Version 2)

2020 ◽  
Author(s):  
Ayman Farag ◽  
Ping Wang ◽  
Mahmoud Ahmed ◽  
Hesham Sadek
Keyword(s):  
Drug Repositioning ◽  
Substrate Binding ◽  
Binding Pocket ◽  
Binding Energies ◽  
Binding Modes ◽  
Substrate Binding Pocket ◽  
Protease Enzyme ◽  
Starting Point ◽  
Approved Drugs ◽  
Fda Approved Drugs

The new strain of Coronaviruses (SARS-CoV-2), and the resulting Covid-19 disease has spread swiftly across the globe after its initial detection in late December 2019 in Wuhan, China, resulting in a pandemic status declaration by WHO within 3 months. Given the heavy toll of this pandemic, researchers are actively testing various strategies including new and repurposed drugs as well as vaccines. In the current brief report, we adopted a repositioning approach using insilico molecular modeling screening using FDA approved drugs with established safety profiles for potential inhibitory effects on Covid-19 virus. We started with structure based drug design by screening more than 2000 FDA approved drugs against Covid-19 virus main protease enzyme (Mpro) substrate-binding pocket focusing on two potential sites (central and terminal sites) to identify potential hits based on their binding energies, binding modes, interacting amino acids, and therapeutic indications. In addition, we elucidate preliminary pharmacophore features for candidates bound to Covid-19 virus Mpro substrate-binding pocket. The top hits bound to the central site of Mpro substrate-binding pocket include antiviral drugs such as Darunavir, Nelfinavir and Saquinavir, some of which are already being tested in Covid-19 patients. Interestingly, one of the most promising hits in our screen is the hypercholesterolemia drug Rosuvastatin. In addition, the top hits bound to the terminal site of Mpro substrate-binding pocket include the anti-asthma drug Montelukast and the anti-histaminic Fexofenadine among others. These results certainly do not confirm or indicate antiviral activity, but can rather be used as a starting point for further in vitro and in vivo testing, either individually or in combination.<br>

scholarly journals Substrate binding modes and anomer selectivity of chitinase A from Vibrio harveyi

2009 ◽  
Vol 2 (4) ◽  
pp. 191-202 ◽  
Author(s):  
Wipa Suginta ◽  
Supansa Pantoom ◽  
Heino Prinz
Keyword(s):  
Vibrio Harveyi ◽  
Substrate Binding ◽  
Binding Modes ◽  
Chitinase A

Switched enantiopreference of Humicola lipase for 2-phenoxyalkanoic acid ester homologs can be rationalized by different substrate binding modes

1999 ◽  
Vol 10 (21) ◽  
pp. 4191-4202 ◽  
Author(s):  
Per Berglund ◽  
Imre Vallikivi ◽  
Linda Fransson ◽  
Heinz Dannacher ◽  
Mats Holmquist ◽  
...  
Keyword(s):  
Acid Ester ◽  
Substrate Binding ◽  
Binding Modes

Structure of a Substrate Complex of Mammalian Cytochrome P450 2C5 at 2.3 Å Resolution:  Evidence for Multiple Substrate Binding Modes†,‡

Biochemistry ◽  
2003 ◽  
Vol 42 (21) ◽  
pp. 6370-6379 ◽  
Author(s):  
Michael R. Wester ◽  
Eric F. Johnson ◽  
Cristina Marques-Soares ◽  
Patrick M. Dansette ◽  
Daniel Mansuy ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Binding Modes ◽  
Substrate Complex ◽  
Multiple Substrate
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