Cleavage Efficiency of the Novel Aspartic Protease Yapsin 1 (Yap3p) Enhanced for Substrates with Arginine Residues Flanking the P1 Site:  Correlation with Electronegative Active-Site Pockets Predicted by Molecular Modeling†,‡

Biochemistry ◽  
1998 ◽  
Vol 37 (9) ◽  
pp. 2768-2777 ◽  
Author(s):  
Vicki Olsen ◽  
Kunchur Guruprasad ◽  
Niamh X. Cawley ◽  
Hao-Chia Chen ◽  
Tom L. Blundell ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Active Site ◽  
Aspartic Protease ◽  
The Novel ◽  
Cleavage Efficiency ◽  
Arginine Residues

Contributions of the substrate-binding arginine residues to maleate-induced closure of the active site of Escherichia coli aspartate aminotransferase

2001 ◽  
Vol 268 (6) ◽  
pp. 1640-1645
Author(s):  
Annelise Matharu ◽  
Hideyuki Hayashi ◽  
Hiroyuki Kagamiyama ◽  
Bruno Maras ◽  
Robert A. John
Keyword(s):  
Escherichia Coli ◽  
Active Site ◽  
Aspartate Aminotransferase ◽  
Substrate Binding ◽  
Arginine Residues

scholarly journals Arginine Residues at the Active Site of Avian Liver Phosphoenolpyruvate Carboxykinase

1989 ◽  
Vol 264 (6) ◽  
pp. 3317-3324
Author(s):  
K C Cheng ◽  
T Nowak
Keyword(s):  
Active Site ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Arginine Residues

Interaction of vanadium metal complexes with protein tyrosine phosphatase-1B enzyme along with identification of active site of enzyme by molecular modeling

2021 ◽  
Vol 126 ◽  
pp. 108499
Author(s):  
Ayub Shaik ◽  
Vani Kondaparthy ◽  
Rambabu Aveli ◽  
M. Vijjulatha ◽  
S. Sree Kanth ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Metal Complexes ◽  
Protein Tyrosine Phosphatase ◽  
Active Site ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Vanadium Metal

scholarly journals Evidence for the importance of arginine residues in pig kidney alkaline phosphatase

1979 ◽  
Vol 181 (1) ◽  
pp. 137-142 ◽  
Author(s):  
M N Woodroofe ◽  
P J Butterworth
Keyword(s):  
Alkaline Phosphatase ◽  
Active Site ◽  
Competitive Inhibitor ◽  
Arginine Residue ◽  
Pig Kidney ◽  
Close Proximity ◽  
Arginine Residues ◽  
Km Value ◽  
Uncompetitive Inhibitor ◽  
Kidney Alkaline Phosphatase

The arginine-specific reagents 2,3-butanedione and phenylglyoxal inactivate pig kidney alkaline phosphatase. As inactivation proceeds there is a progressive fall in Vmax. of the enzyme, but no demonstrable change in the Km value for substrate. Pi, a competitive inhibitor, and AMP, a substrate of the enzyme, protect alkaline phosphatase against the arginine-specific reagents. These effects are explicable by the assumption that the enzyme contains an essential arginine residue at the active site. Protection is also afforded by the uncompetitive inhibitor NADH through a partially competive action against the reagents. Enzyme that has been exposed to the reagents has a decreased sensitivity to NADH inhibition. It is suggested that an arginine residue is important for NADH binding also, although this residue is distinct from that at the catalytic site. The protection given by NADH against loss of activity is indicative of the close proximity of the active and NADH sites.

Role of active site arginine residues in substrate recognition by PPM1A

2021 ◽  
Author(s):  
Itsumi Tani ◽  
Shogo Ito ◽  
Yukiko Shirahata ◽  
Yutaka Matsuyama ◽  
James G. Omichinski ◽  
...  
Keyword(s):  
Active Site ◽  
Substrate Recognition ◽  
Arginine Residues

scholarly journals Molecular modeling and prediction of binding mode and relative binding affinity of Art-Qui-OH with P. falciparum Histo-Aspartic Protease (HAP)

2012 ◽  
Vol 8 (17) ◽  
pp. 827-833 ◽  
Author(s):  
Rajani Kanta Mahapatra ◽  
Niranjan Behera ◽  
Pradeep Kumar Naik
Keyword(s):  
Molecular Modeling ◽  
Binding Affinity ◽  
Binding Mode ◽  
Aspartic Protease ◽  
Modeling And Prediction ◽  
Relative Binding Affinity ◽  
Relative Binding

Molecular Modeling and Active Site Binding Mode Characterization of Aspartate β-Semialdehyde Dehydrogenase Family

2013 ◽  
Vol 32 (4) ◽  
pp. 377-383 ◽  
Author(s):  
Rajender Kumar ◽  
Prabha Garg
Keyword(s):  
Molecular Modeling ◽  
Active Site ◽  
Binding Mode ◽  
Semialdehyde Dehydrogenase ◽  
Site Binding

Functional analysis of box I mutations in yeast site-specific recombinases Flp and R: pairwise complementation with recombinase variants lacking the active-site tyrosine

1992 ◽  
Vol 12 (9) ◽  
pp. 3757-3765
Author(s):  
J W Chen ◽  
B R Evans ◽  
S H Yang ◽  
H Araki ◽  
Y Oshima ◽  
...  
Keyword(s):  
Active Site ◽  
Dna Cleavage ◽  
Substrate Binding ◽  
Point Mutations ◽  
Transfer Reactions ◽  
Strand Transfer ◽  
Site Specific ◽  
Arginine Residues ◽  
Active Site Tyrosine ◽  
Half Site

The site-specific recombinases Flp and R from Saccharomyces cerevisiae and Zygosaccharomyces rouxii, respectively, are related proteins that belong to the yeast family of site-specific recombinases. They share approximately 30% amino acid matches and exhibit a common reaction mechanism that appears to be conserved within the larger integrase family of site-specific recombinases. Two regions of the proteins, designated box I and box II, also harbor a significantly high degree of homology at the nucleotide sequence level. We have analyzed the properties of Flp and R variants carrying point mutations within the box I segment in substrate-binding, DNA cleavage, and full-site and half-site strand transfer reactions. All mutations abolish or seriously diminish recombinase function either at the substrate-binding step or at the catalytic steps of strand cleavage or strand transfer. Of particular interest are mutations of Arg-191 of Flp and R, residues which correspond to one of the two invariant arginine residues of the integrase family. These variant proteins bind substrate with affinities comparable to those of the corresponding wild-type recombinases. Among the binding-competent variants, only Flp(R191K) is capable of efficient substrate cleavage in a full recombination target. However, this protein does not cleave a half recombination site and fails to complete strand exchange in a full site. Strikingly, the Arg-191 mutants of Flp and R can be rescued in half-site strand transfer reactions by a second point mutant of the corresponding recombinase that lacks its active-site tyrosine (Tyr-343). Similarly, Flp and R variants of Cys-189 and Flp variants at Asp-194 and Asp-199 can also be complemented by the corresponding Tyr-343-to-phenylalanine recombinase mutant.

scholarly journals Halogen Bond Interactions of Novel HIV-1 Protease Inhibitors (PI) (GRL-001-15 and GRL-003-15) with the Flap of Protease Are Critical for Their Potent Activity against Wild-Type HIV-1 and Multi-PI-Resistant Variants

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Shin-ichiro Hattori ◽  
Hironori Hayashi ◽  
Haydar Bulut ◽  
Kalapala Venkateswara Rao ◽  
Prasanth R. Nyalapatla ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protease Inhibitors ◽  
Active Site ◽  
Fluorine Atom ◽  
Halogen Bond ◽  
The Novel ◽  
Wild Type ◽  
Flap Region ◽  
Hiv 1

ABSTRACTWe generated two novel nonpeptidic HIV-1 protease inhibitors (PIs), GRL-001-15 and GRL-003-15, which contain unique crown-like tetrahydropyranofuran (Crn-THF) and P2′-cyclopropyl-aminobenzothiazole (Cp-Abt) moieties as P2 and P2′ ligands, respectively. GRL-001-15 and GRL-003-15 havemeta-monofluorophenyl andpara-monofluorophenyl at the P1 site, respectively, exert highly potent activity against wild-type HIV-1 with 50% effective concentrations (EC50s) of 57 and 50 pM, respectively, and have favorable cytotoxicity profiles with 50% cytotoxic concentrations (CC50s) of 38 and 11 μM, respectively. The activity of GRL-001-15 against multi-PI-resistant HIV-1 variants was generally greater than that of GRL-003-15. The EC50of GRL-001-15 against an HIV-1 variant that was highly resistant to multiple PIs, including darunavir (DRV) (HIV-1DRVRP30), was 0.17 nM, and that of GRL-003-15 was 3.3 nM, while DRV was much less active, with an EC50of 216 nM. The emergence of HIV-1 variants resistant to GRL-001-15 and GRL-003-15 was significantly delayed compared to that of variants resistant to selected PIs, including DRV. Structural analyses of wild-type protease (PRWT) complexed with the novel PIs revealed that GRL-001-15’smeta-fluorine atom forms halogen bond interactions (2.9 and 3.0 Å) with Gly49 and Ile50, respectively, of the protease flap region and with Pro81′ (2.7 and 3.2 Å), which is located close to the protease active site, and that two fluorine atoms of GRL-142-13 form multiple halogen bond interactions with Gly49, Ile50, Pro81′, Ile82′, and Arg8′. In contrast, GRL-003-15 forms halogen bond interactions with Pro81′ alone, suggesting that the reduced antiviral activity of GRL-003-15 is due to the loss of the interactions with the flap region.

Sign in / Sign up

Export Citation Format

Share Document