Effect of pH on the activities of penicillopepsin and Rhizopus pepsin and a proposal for the productive substrate binding mode in penicillopepsin

Biochemistry ◽  
1984 ◽  
Vol 23 (4) ◽  
pp. 635-643 ◽  
Author(s):  
Theo Hofmann ◽  
Robert S. Hodges ◽  
Michael N. G. James
Keyword(s):  
Substrate Binding ◽  
Binding Mode ◽  
Effect Of Ph

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.

Predictable Selectivity in Remote C−H Oxidation of Steroids: Analysis of Substrate Binding Mode

2020 ◽  
Vol 59 (31) ◽  
pp. 12703-12708 ◽  
Author(s):  
Giorgio Olivo ◽  
Giorgio Capocasa ◽  
Barbara Ticconi ◽  
Osvaldo Lanzalunga ◽  
Stefano Di Stefano ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Binding Mode

Fine-tuning of the substrate binding mode to enhance the catalytic efficiency of an ortho-haloacetophenone-specific carbonyl reductase

2020 ◽  
Vol 10 (8) ◽  
pp. 2462-2472
Author(s):  
Aipeng Li ◽  
Xue Li ◽  
Wei Pang ◽  
Qing Tian ◽  
Ting Wang ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Catalytic Efficiency ◽  
Binding Mode ◽  
Carbonyl Reductase ◽  
Fine Tuning

Fine-tuning of the substrate binding mode was successfully applied for enhancing the catalytic efficiency of an ortho-haloacetophenone-specific carbonyl reductase.

Structure of a gut microbial diltiazem-metabolizing enzyme suggests possible substrate binding mode

2020 ◽  
Vol 527 (3) ◽  
pp. 799-804
Author(s):  
Shuyu Zhou ◽  
Tzu-Ping Ko ◽  
Jian-Wen Huang ◽  
Weidong Liu ◽  
Yingying Zheng ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Binding Mode ◽  
Metabolizing Enzyme

A Nitrogenase Cluster Model [Fe8S6O] with an Oxygen Unsymmetrically Bridging Two Proto-Fe4S3 Cubes: Relevancy to the Substrate Binding Mode of the FeMo Cofactor

2012 ◽  
Vol 51 (21) ◽  
pp. 11217-11219 ◽  
Author(s):  
Shun Ohta ◽  
Yasuhiro Ohki ◽  
Takayoshi Hashimoto ◽  
Roger E. Cramer ◽  
Kazuyuki Tatsumi
Keyword(s):  
Cluster Model ◽  
Substrate Binding ◽  
Binding Mode ◽  
Femo Cofactor

scholarly journals The effect of pH on the kinetics of arylsulphatases A and B

1983 ◽  
Vol 213 (3) ◽  
pp. 603-607 ◽  
Author(s):  
C O'Fagain ◽  
B M Butler ◽  
T J Mantle
Keyword(s):  
Enzyme Activity ◽  
Rat Liver ◽  
Substrate Binding ◽  
Acid Base ◽  
Effect Of Ph ◽  
Substrate Complex ◽  
Enzyme Substrate ◽  
General Acid ◽  
Kinetics Of

The effect of pH on the kinetics of rat liver arylsulphatases A and B is very similar and shows that two groups with pK values of 4.4-4.5 and 5.7-5.8 are important for enzyme activity. Substrate binding has no effect on the group with a pK of 4.4-4.5; however, the pK of the second group is shifted to 7.1-7.5 in the enzyme-substrate complex. An analysis of the effect of pH on the Ki for sulphate inhibition suggests that HSO4-is the true product. A model is proposed that involves the two ionizing groups identified in the present study in a concerted general acid-base-catalysed mechanism.

scholarly journals Substrate Binding Mode and Its Implication on Drug Design for Botulinum Neurotoxin A

2008 ◽  
Vol 4 (9) ◽  
pp. e1000165 ◽  
Author(s):  
Desigan Kumaran ◽  
Richa Rawat ◽  
S. Ashraf Ahmed ◽  
Subramanyam Swaminathan
Keyword(s):  
Drug Design ◽  
Botulinum Neurotoxin ◽  
Substrate Binding ◽  
Binding Mode ◽  
Botulinum Neurotoxin A
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