scholarly journals The dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae contains two active-site histidine residues

2008 ◽  
Vol 14 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Danuta M. Gillner ◽  
David L. Bienvenue ◽  
Boguslaw P. Nocek ◽  
Andrzej Joachimiak ◽  
Vincentos Zachary ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Active Site ◽  
Diaminopimelic Acid ◽  
Histidine Residues ◽  
Active Site Histidine

scholarly journals Identification of Active-Site Histidine Residues of a Self-Incompatibility Ribonuclease from a Wild Tomato

1997 ◽  
Vol 115 (4) ◽  
pp. 1421-1429 ◽  
Author(s):  
S. Parry ◽  
E. Newbigin ◽  
G. Currie ◽  
A. Bacic ◽  
D. Oxley
Keyword(s):  
Active Site ◽  
Self Incompatibility ◽  
Histidine Residues ◽  
Wild Tomato ◽  
Active Site Histidine

scholarly journals Malate dehydrogenase of the cytosol. Ionizations of the enzyme-reduced-coenzyme complex and a comparison with lactate dehydrogenase

1978 ◽  
Vol 173 (2) ◽  
pp. 597-605 ◽  
Author(s):  
A Lodola ◽  
D M Parker ◽  
R Jeck ◽  
J J Holbrook
Keyword(s):  
Lactate Dehydrogenase ◽  
Malate Dehydrogenase ◽  
Active Site ◽  
Histidine Residue ◽  
Histidine Residues ◽  
Coenzyme Binding ◽  
Active Site Histidine

1. The pH-dependencies of the binding of NADH and reduced nicotinamide–benzimidazole dinucleotide to pig heart cytoplasmic malate dehydrogenase and lactate dehydrogenase are reported. 2. Two ionizing groups were observed in the binding of both reduced coenzymes to lactate dehydrogenase. One group, with pKa in the range 6.3–6.7, is the active-site histidine residue and its deprotonation weakens binding of reduced coenzyme 3-fold. Binding of both coenzymes is decreased to zero when a second group, of pKa 8.9, deprotonates. This group is not cysteine-165.3. Only one ionization is required to characterize the binding of the two reduced coenzymes to malate dehydrogenase. The group involved appears to be the active-site histidine residue, since its ethoxycarbonylation inhibits the enzyme and abolishes binding of reduced coenzyme. Binding of either reduced coenzyme increases the pKa of the group from 6.4 to 7.4, and deprotonation of the group is accompanied by a 10-fold weakening of coenzyme binding. 4. Two reactive histidine residues were detected per malate dehydrogenase dimer. 5. A mechanism which emphasizes the homology between the two enzymes is presented.

Inhibitor Binding Modulates Protonation States in the Active Site of SARS-CoV-2 Main Protease

2021 ◽  
Author(s):  
Daniel W. Kneller ◽  
Gwyndalyn Phillips ◽  
Kevin L. Weiss ◽  
Qiu Zhang ◽  
Leighton Coates ◽  
...  
Keyword(s):  
Active Site ◽  
Rational Drug Design ◽  
Inhibitor Binding ◽  
Histidine Residues ◽  
Main Protease ◽  
Rational Drug ◽  
Ligand Free ◽  
Essential Enzyme ◽  
Neutron Protein Crystallography ◽  
Active Site Histidine

ABSTRACTThe main protease (3CL Mpro) from SARS-CoV-2, the virus that causes COVID-19, is an essential enzyme for viral replication with no human counterpart, making it an attractive drug target. Although drugs have been developed to inhibit the proteases from HIV, hepatitis C and other viruses, no such therapeutic is available to inhibit the main protease of SARS-CoV-2. To directly observe the protonation states in SARS-CoV-2 Mpro and to elucidate their importance in inhibitor binding, we determined the structure of the enzyme in complex with the α-ketoamide inhibitor telaprevir using neutron protein crystallography at near-physiological temperature. We compared protonation states in the inhibitor complex with those determined for a ligand-free neutron structure of Mpro. This comparison revealed that three active-site histidine residues (His41, His163 and His164) adapt to ligand binding, altering their protonation states to accommodate binding of telaprevir. We suggest that binding of other α-ketoamide inhibitors can lead to the same protonation state changes of the active site histidine residues. Thus, by studying the role of active site protonation changes induced by inhibitors we provide crucial insights to help guide rational drug design, allowing precise tailoring of inhibitors to manipulate the electrostatic environment of SARS-CoV-2 Mpro.

Contribution of the Active Site Histidine Residues of Ribonuclease A to Nucleic Acid Binding†

Biochemistry ◽  
2001 ◽  
Vol 40 (16) ◽  
pp. 4949-4956 ◽  
Author(s):  
Chiwook Park ◽  
L. Wayne Schultz ◽  
Ronald T. Raines
Keyword(s):  
Nucleic Acid ◽  
Active Site ◽  
Ribonuclease A ◽  
Nucleic Acid Binding ◽  
Histidine Residues ◽  
Active Site Histidine

scholarly journals Alkylation and Identification of the Histidine Residues at the Active Site of Ribonuclease

1963 ◽  
Vol 238 (7) ◽  
pp. 2413-2420 ◽  
Author(s):  
Arthur M. Crestfield ◽  
William H. Stein ◽  
Stanford Moore
Keyword(s):  
Active Site ◽  
Histidine Residues

scholarly journals Properties and Conformation of the Histidine Residues at the Active Site of Ribonuclease

1963 ◽  
Vol 238 (7) ◽  
pp. 2421-2428 ◽  
Author(s):  
Arthur M. Crestfield ◽  
William H. Stein ◽  
Stanford Moore
Keyword(s):  
Active Site ◽  
Histidine Residues

Structure and activity of phosphoglycerate mutase

1981 ◽  
Vol 293 (1063) ◽  
pp. 121-130 ◽  
Keyword(s):  
Active Site ◽  
Transfer Reaction ◽  
Chemical Kinetic ◽  
Phosphoglycerate Mutase ◽  
Phosphoryl Transfer ◽  
X Ray ◽  
Histidine Residues ◽  
Ping Pong ◽  
Available Information ◽  
Structure And Activity

The structure of yeast phosphoglycerate mutase determined by X-ray crystallographic and amino acid sequence studies has been interpreted in terms of the chemical, kinetic and mechanistic observations made on this enzyme. There are two histidine residues at the active site, with imidazole groups almost parallel to each other and approximately 0.4 nm apart, positioned close to the 2 and 3 positions of the substrate. The simplest interpretation of the available information suggests that a ping-pong type mechanism operates in which at least one of these histidine residues participates in the phosphoryl transfer reaction. The flexible C-terminal region also plays an important role in the enzymic reaction.

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