Alternate Substrate Binding Modes to Two Mutant (D98N and H255N) Forms of Nitrite Reductase fromAlcaligenes faecalisS-6:  Structural Model of a Transient Catalytic Intermediate†,‡

Biochemistry ◽  
2001 ◽  
Vol 40 (31) ◽  
pp. 9132-9141 ◽  
Author(s):  
Martin J. Boulanger ◽  
Michael E. P. Murphy
Keyword(s):  
Nitrite Reductase ◽  
Structural Model ◽  
Substrate Binding ◽  
Binding Modes ◽  
Alternate Substrate

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

Understanding the distinguishable structural and functional features in zebrafish TLR3 and TLR22, and their binding modes with fish dsRNA viruses: an exploratory structural model analysis

Amino Acids ◽  
2014 ◽  
Vol 47 (2) ◽  
pp. 381-400 ◽  
Author(s):  
Bikash Ranjan Sahoo ◽  
Manas Ranjan Dikhit ◽  
Gopal Krushna Bhoi ◽  
Jitendra Maharana ◽  
Santosh Kumar Lenka ◽  
...  
Keyword(s):  
Structural Model ◽  
Model Analysis ◽  
Binding Modes ◽  
Functional Features ◽  
Dsrna Viruses

The nature of the substrate binding site in copper nitrite reductase from Achromobacter xylosoxidans (AxNiR)

1995 ◽  
Vol 59 (2-3) ◽  
pp. 711
Author(s):  
R.W. Strange ◽  
J.G. Grossmann ◽  
F.E. Dodd ◽  
S.S. Hasnain ◽  
Z.H.L. Abraham ◽  
...  
Keyword(s):  
Binding Site ◽  
Nitrite Reductase ◽  
Substrate Binding ◽  
Achromobacter Xylosoxidans ◽  
Substrate Binding Site

Substrate Binding to a Nitrite Reductase Induces a Spin Transition

2010 ◽  
Vol 114 (16) ◽  
pp. 5563-5566 ◽  
Author(s):  
Gabriel Martins ◽  
Luisa Rodrigues ◽  
Filipa M. Cunha ◽  
Daniela Matos ◽  
Peter Hildebrandt ◽  
...  
Keyword(s):  
Nitrite Reductase ◽  
Substrate Binding ◽  
Spin Transition

Crystal structure of 4-hydroxybutyrate CoA-transferase from Clostridium aminobutyricum

2009 ◽  
Vol 390 (12) ◽  
Author(s):  
Sofia Macieira ◽  
Jin Zhang ◽  
Milko Velarde ◽  
Wolfgang Buckel ◽  
Albrecht Messerschmidt
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Structural Model ◽  
Substrate Binding ◽  
Anaerobic Bacteria ◽  
Shewanella Oneidensis ◽  
Site Directed Mutagenesis ◽  
Highly Active ◽  
Coa Transferase ◽  
Facultative Anaerobic Bacteria

Abstract4-Hydroxybutyrate CoA-transferases (4-HB-CoAT) takes part in the fermentation of 4-aminobutyrate to ammonia, acetate, and butyrate in anaerobic bacteria such asClostridium aminobutyricumandPorphyromonas gingivalisor facultative anaerobic bacteria such asShewanella oneidensis. Site-directed mutagenesis of the highly active enzyme has identified the catalytic glutamate residue as E238. Crystal structure of this enzyme has been determined at a resolution of 1.85 Å. The 438-amino acid residue polypeptide chain folds into two topologically similar domains with an open α/β-fold, which is also found in other CoAT family I and family II members. The data indicate that the members of CoAT families I and II are closely related; the latter only lacking the catalytic glutamate residue. A putative co-substrate binding site for the 4-HB-CoAT was identified, in which a 4-hydroxybutyrate molecule has been modeled. This site is also responsible for binding the acetyl group of acetyl-CoA or the succinyl group of succinyl-CoA in succinyl-CoA:3-oxoacid CoA-transferase from mammalian mitochondria. Mutations of relevant active site amino acid residues have been produced and their activities tested to corroborate the proposed structural model for substrate binding. 4-HB-CoAT fromC. aminobutyricumrepresents the only functionally characterized 4-HB-CoAT present in the structural database.

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 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.

scholarly journals Molecular determinant of substrate binding and specificity of cytochrome P450 2J2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Liang Xu ◽  
Liao Y. Chen
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Active Site ◽  
Structural Model ◽  
Substrate Binding ◽  
Conformational Dynamics ◽  
Structural Basis ◽  
Molecular Determinant ◽  
Dynamics Simulations

AbstractCytochrome P450 2J2 (CYP2J2) is responsible for the epoxidation of endogenous arachidonic acid, and is involved in the metabolism of exogenous drugs. To date, no crystal structure of CYP2J2 is available, and the proposed structural basis for the substrate recognition and specificity in CYP2J2 varies with the structural models developed using different computational protocols. In this study, we developed a new structural model of CYP2J2, and explored its sensitivity to substrate binding by molecular dynamics simulations of the interactions with chemically similar fluorescent probes. Our results showed that the induced-fit binding of these probes led to the preferred active poses ready for the catalysis by CYP2J2. Divergent conformational dynamics of CYP2J2 due to the binding of each probe were observed. However, a stable hydrophobic clamp composed of residues I127, F310, A311, V380, and I487 was identified to restrict any substrate access to the active site of CYP2J2. Molecular docking of a series of compounds including amiodarone, astemizole, danazol, ebastine, ketoconazole, terfenadine, terfenadone, and arachidonic acid to CYP2J2 confirmed the role of those residues in determining substrate binding and specificity of CYP2J2. In addition to the flexibility of CYP2J2, the present work also identified other factors such as electrostatic potential in the vicinity of the active site, and substrate strain energy and property that have implications for the interpretation of CYP2J2 metabolism.

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>

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