Recent theoretical predictions of the active site for the observed forms in the catalytic cycle of Ni-Fe hydrogenase

2001 ◽  
Vol 6 (4) ◽  
pp. 467-473 ◽  
Author(s):  
Hua-Jun Fan ◽  
Michael B. Hall
Keyword(s):  
Active Site ◽  
Catalytic Cycle ◽  
Theoretical Predictions

scholarly journals Local frustration determines loop opening during the catalytic cycle of an oxidoreductase

2019 ◽  
Author(s):  
Lukas L. Stelzl ◽  
Despoina A.I. Mavridou ◽  
Emmanuel Saridakis ◽  
Diego Gonzalez ◽  
Andrew J. Baldwin ◽  
...  
Keyword(s):  
Active Site ◽  
Binding Sites ◽  
Protein Function ◽  
Catalytic Cycle ◽  
Biomolecular Recognition ◽  
Competing Interactions ◽  
Protein Binding Sites ◽  
Loop Region ◽  
Cysteine Thiols ◽  
Small Chemical

AbstractLocal structural frustration, the existence of mutually exclusive competing interactions, may explain why some proteins are dynamic while others are rigid. Frustration is thought to underpin biomolecular recognition and the flexibility of protein binding sites. Here we show how a small chemical modification, the oxidation of two cysteine thiols to a disulfide bond, during the catalytic cycle of the N-terminal domain of the key bacterial oxidoreductase DsbD (nDsbD), introduces frustration ultimately influencing protein function. In oxidized nDsbD, local frustration disrupts the packing of the protective cap-loop region against the active site allowing loop opening. By contrast, in reduced nDsbD the cap loop is rigid, always protecting the active-site thiols from the oxidizing environment of the periplasm. Our results point towards an intricate coupling between the dynamics of the active-site cysteines and of the cap loop which modulates the association reactions of nDsbD with its partners resulting in optimized protein function.

A Nickel Hydride Complex in the Active Site of Methyl-Coenzyme M Reductase: Implications for the Catalytic Cycle

2008 ◽  
Vol 130 (33) ◽  
pp. 10907-10920 ◽  
Author(s):  
Jeffrey Harmer ◽  
Cinzia Finazzo ◽  
Rafal Piskorski ◽  
Sieglinde Ebner ◽  
Evert C. Duin ◽  
...  
Keyword(s):  
Active Site ◽  
Catalytic Cycle ◽  
Coenzyme M ◽  
Hydride Complex ◽  
Nickel Hydride ◽  
Methyl Coenzyme M Reductase

scholarly journals Structure ofEscherichia coliGrx2 in complex with glutathione: a dual-function hybrid of glutaredoxin and glutathioneS-transferase

2014 ◽  
Vol 70 (7) ◽  
pp. 1907-1913 ◽  
Author(s):  
Jun Ye ◽  
S. Venkadesh Nadar ◽  
Jiaojiao Li ◽  
Barry P. Rosen
Keyword(s):  
Escherichia Coli ◽  
Electron Donor ◽  
Active Site ◽  
Active Sites ◽  
Catalytic Cycle ◽  
Dual Function ◽  
Active Site Residues ◽  
E Coli ◽  
Arsenate Reduction ◽  
Gst Activity

The structure of glutaredoxin 2 (Grx2) fromEscherichia colico-crystallized with glutathione (GSH) was solved at 1.60 Å resolution. The structure of a mutant with the active-site residues Cys9 and Cys12 changed to serine crystallized in the absence of glutathione was solved to 2.4 Å resolution. Grx2 has an N-terminal domain characteristic of glutaredoxins, and the overall structure is congruent with the structure of glutathioneS-transferases (GSTs). Purified Grx2 exhibited GST activity. Grx2, which is the physiological electron donor for arsenate reduction byE. coliArsC, was docked with ArsC. The docked structure could be fitted with GSH bridging the active sites of the two proteins. It is proposed that Grx2 is a novel Grx/GST hybrid that functions in two steps of the ArsC catalytic cycle: as a GST it catalyzes glutathionylation of the ArsC–As(V) intermediate and as a glutaredoxin it catalyzes deglutathionylation of the ArsC–As(III)–SG intermediate.

Conformational Changes in the Active Site Loops of Dihydrofolate Reductase during the Catalytic Cycle†

Biochemistry ◽  
2004 ◽  
Vol 43 (51) ◽  
pp. 16046-16055 ◽  
Author(s):  
Rani P. Venkitakrishnan ◽  
Eduardo Zaborowski ◽  
Dan McElheny ◽  
Stephen J. Benkovic ◽  
H. Jane Dyson ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Conformational Changes ◽  
Active Site ◽  
Catalytic Cycle

scholarly journals Nucleotide-mediated allosteric regulation of bifunctional Rel enzymes

2019 ◽  
Author(s):  
Hedvig Tamman ◽  
Katleen Van Nerom ◽  
Hiraku Takada ◽  
Niels Vandenberk ◽  
Daniel Scholl ◽  
...  
Keyword(s):  
Active Site ◽  
Molecular Level ◽  
Catalytic Cycle ◽  
Catalytic Domains ◽  
Allosteric Mechanism ◽  
Switch Mechanism ◽  
Futile Cycles ◽  
Hydrolysis Of ◽  
Pyrophosphate Hydrolysis ◽  
Synthesis And Degradation

Bifunctional Rel stringent factors, the most broadly distributed class of RSHs, are ribosome-associated enzymes that transfer a pyrophosphate group from ATP onto the 3′ of GTP or GDP to synthesize (p)ppGpp and also catalyse the 3′ pyrophosphate hydrolysis of the alarmone to degrade it. The precise regulation of these enzymes seems to be a complex allosteric mechanism, and despite decades of research, it is unclear how the two opposing activities of Rel are controlled at the molecular level. Here we show that a stretch/recoil guanosine-switch mechanism controls the catalytic cycle of T. thermophilus Rel (RelTf). The binding of GDP/ATP stretches apart the NTD catalytic domains of RelTf (RelTtNTD) activating the synthetase domain and allosterically blocking the hydrolase active site. Conversely, binding of ppGpp unlocks the hydrolase domain and triggers recoil of both NTDs, which partially buries the synthetase active site and precludes the binding of synthesis precursors. This allosteric mechanism acts as an activity switch preventing futile cycles of alarmone synthesis and degradation.

scholarly journals Structural Insights into the Catalytic Mechanism of Granzyme B upon Substrate and Inhibitor Binding

2021 ◽  
Author(s):  
Neha Tripathi ◽  
Richard Danger ◽  
Mélanie Chesneau ◽  
Sophie Brouard ◽  
Adèle Laurent
Keyword(s):  
Active Site ◽  
Serine Proteases ◽  
Catalytic Mechanism ◽  
Granzyme B ◽  
Salt Bridge ◽  
Catalytic Triad ◽  
Catalytic Cycle ◽  
Major Step ◽  
Dynamics Simulations ◽  
First Time

Human granzyme B (hGzmB), which is present in various immune cells, has attracted much attention due to its role in various pathophysiological conditions. The hGzmB activity is triggered at a catalytic triad (His59, Asp103, Ser198), cleaving its specific substrates. To date, the drug design strategy against hGzmB mainly targets the catalytic triad, which causes the non-specificity problem of inhibitors due to the highly conserved active site in serine proteases. In the present work, microsecond classical molecular dynamics simulations are devoted to exploring the structural dynamics of the hGzmB catalytic cycle in the presence of Ac-IEPD-AMC, a known substrate (active hGzmB), and Ac-IEPD-CHO, a known inhibitor (inactive hGzmB). By comparing active and inactive forms of hGzmB in the six different stages of the hGzmB catalytic cycle, we revealed, for the very first time, an additional network of interactions involving Arg216, a residue located outside the conventional binding site. Upon activation, the His59∙∙∙Asp103 hydrogen bond is broken due to the formation of the Asp103∙∙∙Arg216 salt bridge, expanding the active site to facilitate the substrate-binding. On the contrary, the binding of inhibitor Ac-IEPD-CHO to hGzmB prevents the Arg216-mediated interactions within the catalytic triad, thus preventing hGzmB activity. In silico Arg216Ala mutation confirms the role of Arg216 in enzyme activity, as the substrate Ac-IEPD-AMC failed to bind to the mutated hGzmB. Importantly, as Arg216 is not conserved amongst the various granzymes, the current findings can be a major step to guide the design of hGzmB specific therapeutics.

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