Design of a small peptide-based proteinase inhibitor by modeling the active-site region of barley chymotrypsin inhibitor 2

Biochemistry ◽  
1991 ◽  
Vol 30 (44) ◽  
pp. 10717-10721 ◽  
Author(s):  
Robin J. Leatherbarrow ◽  
Henryk J. Salacinski
Keyword(s):  
Active Site ◽  
Proteinase Inhibitor ◽  
Small Peptide ◽  
Chymotrypsin Inhibitor ◽  
Chymotrypsin Inhibitor 2 ◽  
Active Site Region

Molecular insight into chymotrypsin inhibitor 2 resisting proteolytic degradation

2019 ◽  
Vol 21 (9) ◽  
pp. 5049-5058
Author(s):  
Wanqing Wei ◽  
Yani Chen ◽  
Daiqian Xie ◽  
Yanzi Zhou
Keyword(s):  
Free Energy ◽  
Active Site ◽  
Hydrolysis Rate ◽  
Proteolytic Degradation ◽  
Chymotrypsin Inhibitor ◽  
Chymotrypsin Inhibitor 2 ◽  
Insight Into

Water enters the active site at the EA2 state, so the free energy at EA2 determines the relative hydrolysis rate.

scholarly journals Activity of linked HIV-1 proteinase dimers containing mutations in the active site region

1996 ◽  
Vol 9 (11) ◽  
pp. 997-1003 ◽  
Author(s):  
Péter Bagossi ◽  
Yin-Shyun E. Cheng ◽  
Stephen Oroszlan ◽  
József Tözsér
Keyword(s):  
Active Site ◽  
Active Site Region ◽  
Hiv 1

scholarly journals A crystallographic study of the Toho-1 β-lactamase acylation mechanism

2014 ◽  
Vol 70 (a1) ◽  
pp. C1207-C1207
Author(s):  
Leighton Coates
Keyword(s):  
Hydrogen Bonding ◽  
Transition State ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Substrate Binding ◽  
Ligand Complex ◽  
Transition State Analog ◽  
Hydrogen Bonding Interactions ◽  
Active Site Region ◽  
Neutron Crystallography

β-lactam antibiotics have been used effectively over several decades against many types of highly virulent bacteria. The predominant cause of resistance to these antibiotics in Gram-negative bacterial pathogens is the production of serine β-lactamase enzymes. A key aspect of the class A serine β-lactamase mechanism that remains unresolved and controversial is the identity of the residue acting as the catalytic base during the acylation reaction. Multiple mechanisms have been proposed for the formation of the acyl-enzyme intermediate that are predicated on understanding the protonation states and hydrogen-bonding interactions among the important residues involved in substrate binding and catalysis of these enzymes. For resolving a controversy of this nature surrounding the catalytic mechanism, neutron crystallography is a powerful complement to X-ray crystallography that can explicitly determine the location of deuterium atoms in proteins, thereby directly revealing the hydrogen-bonding interactions of important amino acid residues. Neutron crystallography was used to unambiguously reveal the ground-state active site protonation states and the resulting hydrogen-bonding network in two ligand-free Toho-1 β-lactamase mutants which provided remarkably clear pictures of the active site region prior to substrate binding and subsequent acylation [1,2] and an acylation transition-state analog, benzothiophene-2-boronic acid (BZB), which was also isotopically enriched with 11B. The neutron structure revealed the locations of all deuterium atoms in the active site region and clearly indicated that Glu166 is protonated in the BZB transition-state analog complex. As a result, the complete hydrogen-bonding pathway throughout the active site region could then deduced for this protein-ligand complex that mimics the acylation tetrahedral intermediate [3].

scholarly journals Digital dissection of arsenate reductase enzyme from an arsenic hyperccumulating fern Pteris vittata

2016 ◽  
Author(s):  
Zarrin Basharat ◽  
Deeba Noreen Baig ◽  
Azra Yasmin
Keyword(s):  
Neural Network ◽  
Active Site ◽  
Tertiary Structure ◽  
Pteris Vittata ◽  
Arsenate Reductase ◽  
Dynamics Simulation ◽  
Reduction Mechanism ◽  
Arsenic Reduction ◽  
Secondary And Tertiary Structure ◽  
Active Site Region

Action of arsenate reductase is crucial for the survival of an organism in arsenic polluted area. Pteris vittata, also known as Chinese ladder brake, was the first identified arsenic hyperaccumulating fern with the capability to convert [As(V)] to arsenite [As(III)]. This study aims at sequence analysis of the most important protein of the arsenic reduction mechanism in this specie. Phosphorylation potential of the protein along with possible interplay of phosphorylation with O-β-GlcNAcylation was predicted using neural network based webservers. Secondary and tertiary structure of arsenate reductase was then analysed. Active site region of the protein comprised a rhodanese-like domain. Cursory dynamics simulation revealed that folds remained conserved in the rhodanese main but variations were observed in the structure in other regions. This information sheds light on the various characteristics of the protein and may be useful to enzymologists working on the improvement of its traits for arsenic reduction.

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