The molecular mechanism of the open–closed protein conformational cycle transitions and coupled substrate binding, activation and product release events in lysine 5,6-aminomutase

2016 ◽  
Vol 52 (38) ◽  
pp. 6399-6402 ◽  
Author(s):  
Hsin-Hsi Lo ◽  
Hsin-Hua Lin ◽  
Amarendra Nath Maity ◽  
Shyue-Chu Ke
Keyword(s):  
Molecular Mechanism ◽  
Bond Cleavage ◽  
Substrate Binding ◽  
Closed Cycle ◽  
Product Release

The contributions of Lys370α and Asp298α to the critical Co–C bond cleavage trigger and open–closed cycle transitions of lysine 5,6-aminomutase.

scholarly journals Product inhibition studies on bovine liver carbamoyl phosphate synthetase

1974 ◽  
Vol 141 (3) ◽  
pp. 817-824 ◽  
Author(s):  
Keith R. F. Elliott ◽  
Keith F. Tipton
Keyword(s):  
Inorganic Phosphate ◽  
Substrate Binding ◽  
Inorganic Ions ◽  
Bovine Liver ◽  
Product Inhibition ◽  
Carbamoyl Phosphate Synthetase ◽  
Carbamoyl Phosphate ◽  
Product Release ◽  
Proposed Model ◽  
Inhibition Studies

A study of the product-inhibition patterns of carbamoyl phosphate synthetase from bovine liver is reported. Inhibition by adenosine, AMP and inorganic ions is also reported. The results are in agreement with the previously proposed model in which the order of substrate binding is ATPMg, followed by HCO3−, ATPMg and NH4+. The order of product release on the basis of the reported results is carbamoyl phosphate, followed by ADPMg, ADPMg and inorganic phosphate.

scholarly journals The substrate-binding cap of the UDP-diacylglucosamine pyrophosphatase LpxH is highly flexible, enabling facile substrate binding and product release

2018 ◽  
Vol 293 (21) ◽  
pp. 7969-7981 ◽  
Author(s):  
Thomas E. Bohl ◽  
Pek Ieong ◽  
John K. Lee ◽  
Thomas Lee ◽  
Jayakanth Kankanala ◽  
...  
Keyword(s):  
Rational Design ◽  
Substrate Binding ◽  
Flexible Substrate ◽  
Binding Mode ◽  
Antibiotic Development ◽  
Product Release ◽  
Outer Leaflet ◽  
Hydrogen Deuterium ◽  
Dynamics Simulations ◽  
Secondary Membrane

Gram-negative bacteria are surrounded by a secondary membrane of which the outer leaflet is composed of the glycolipid lipopolysaccharide (LPS), which guards against hydrophobic toxins, including many antibiotics. Therefore, LPS synthesis in bacteria is an attractive target for antibiotic development. LpxH is a pyrophosphatase involved in LPS synthesis, and previous structures revealed that LpxH has a helical cap that binds its lipid substrates. Here, crystallography and hydrogen–deuterium exchange MS provided evidence for a highly flexible substrate-binding cap in LpxH. Furthermore, molecular dynamics simulations disclosed how the helices of the cap may open to allow substrate entry. The predicted opening mechanism was supported by activity assays of LpxH variants. Finally, we confirmed biochemically that LpxH is inhibited by a previously identified antibacterial compound, determined the potency of this inhibitor, and modeled its binding mode in the LpxH active site. In summary, our work provides evidence that the substrate-binding cap of LpxH is highly dynamic, thus allowing for facile substrate binding and product release between the capping helices. Our results also pave the way for the rational design of more potent LpxH inhibitors.

Substrate Binding, Catalysis, and Product Release

2004 ◽  
pp. 123-126
Author(s):  
W. Wallace Cleland
Keyword(s):  
Substrate Binding ◽  
Product Release

The Dinuclear Zn(II) Complex Catalyzed Cyclization of a Series of 2-Hydroxypropyl Aryl Phosphate RNA Models:  Progressive Change in Mechanism from Rate-Limiting P−O Bond Cleavage to Substrate Binding

2007 ◽  
Vol 129 (51) ◽  
pp. 16238-16248 ◽  
Author(s):  
Shannon E. Bunn ◽  
C. Tony Liu ◽  
Zhong-Lin Lu ◽  
Alexei A. Neverov ◽  
R. Stan Brown
Keyword(s):  
Bond Cleavage ◽  
Substrate Binding ◽  
Progressive Change ◽  
Rate Limiting

scholarly journals Conformational change in substrate binding, catalysis and product release: an open and shut case?

FEBS Letters ◽  
2004 ◽  
Vol 567 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Alex Gutteridge ◽  
Janet Thornton
Keyword(s):  
Conformational Change ◽  
Substrate Binding ◽  
Product Release

Substrate Binding, Catalysis, and Product Release

2013 ◽  
pp. 347-349
Author(s):  
W.W. Cleland
Keyword(s):  
Substrate Binding ◽  
Product Release

Polymer Gel Phase Transition: The Molecular Mechanism of Product Release in Mucin Secretion?

1992 ◽  
pp. 671-681 ◽  
Author(s):  
Pedro Verdugo ◽  
Ingrith Deyrup-Olsen ◽  
Arthur W. Martin ◽  
Daniel L. Luchtel
Keyword(s):  
Phase Transition ◽  
Molecular Mechanism ◽  
Polymer Gel ◽  
Mucin Secretion ◽  
Product Release ◽  
Gel Phase

Divalent metal ions control activity and inhibition of protein kinases

Metallomics ◽  
2017 ◽  
Vol 9 (11) ◽  
pp. 1576-1584 ◽  
Author(s):  
Matthias J. Knape ◽  
Mike Ballez ◽  
Nicole C. Burghardt ◽  
Bastian Zimmermann ◽  
Daniela Bertinetti ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Metal Ions ◽  
Protein Kinases ◽  
Substrate Binding ◽  
Divalent Metal ◽  
Catalytic Cycle ◽  
Divalent Metal Ions ◽  
Control Activity ◽  
Product Release

Metals like Zn2+ and Mn2+ can assist in the catalytic cycle of a protein kinase by facilitating substrate binding and phosphotransfer, however, in contrast to Mg2+ they also hamper product release.

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