scholarly journals Structure of theS. aureusPI-Specific Phospholipase C Reveals Modulation of Active Site Access by a Titratable π-Cation Latched Loop

Biochemistry ◽  
2012 ◽  
Vol 51 (12) ◽  
pp. 2579-2587 ◽  
Author(s):  
Rebecca Goldstein ◽  
Jiongjia Cheng ◽  
Boguslaw Stec ◽  
Mary F. Roberts
Keyword(s):  
Phospholipase C ◽  
Active Site ◽  
Site Access

Rational backbone redesign of a fructosyl peptide oxidase to widen its active site access tunnel

2020 ◽  
Vol 117 (12) ◽  
pp. 3688-3698
Author(s):  
Federica Rigoldi ◽  
Stefano Donini ◽  
Archimede Torretta ◽  
Anna Carbone ◽  
Alberto Redaelli ◽  
...  
Keyword(s):  
Active Site ◽  
Site Access ◽  
Fructosyl Peptide Oxidase

Conformation analysis of a surface loop that controls active site access in the GH11 xylanase A from Bacillus subtilis

2011 ◽  
Vol 18 (4) ◽  
pp. 1473-1479 ◽  
Author(s):  
Davi Serradella Vieira ◽  
Richard John Ward
Keyword(s):  
Bacillus Subtilis ◽  
Active Site ◽  
Conformation Analysis ◽  
Surface Loop ◽  
Site Access

A Catalytic Diad Involved in Substrate-Assisted Catalysis:  NMR Study of Hydrogen Bonding and Dynamics at the Active Site of Phosphatidylinositol-Specific Phospholipase C†

Biochemistry ◽  
2001 ◽  
Vol 40 (32) ◽  
pp. 9743-9750 ◽  
Author(s):  
Margret Ryan ◽  
Tun Liu ◽  
Frederick W. Dahlquist ◽  
O. Hayes Griffith
Keyword(s):  
Hydrogen Bonding ◽  
Phospholipase C ◽  
Active Site ◽  
Nmr Study

Probing the Roles of Active Site Residues in Phosphatidylinositol-Specific Phospholipase C fromBacillus cereusby Site-Directed Mutagenesis†

Biochemistry ◽  
1997 ◽  
Vol 36 (42) ◽  
pp. 12802-12813 ◽  
Author(s):  
Claudia S. Gässler ◽  
Margret Ryan ◽  
Tun Liu ◽  
O. Hayes Griffith ◽  
Dirk W. Heinz
Keyword(s):  
Phospholipase C ◽  
Active Site ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Active Site Residues

scholarly journals Tethered Aryl Groups Increase the Activity of Anti-Proliferative Thieno[2,3-b]Pyridines by Targeting a Lipophilic Region in the Active Site of PI-PLC

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2020
Author(s):  
Natalie A. Haverkate ◽  
Euphemia Leung ◽  
Lisa I. Pilkington ◽  
David Barker
Keyword(s):  
Phospholipase C ◽  
Cancer Cell ◽  
Active Site ◽  
Proliferative Activity ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Unsaturated Ketone ◽  
Aryl Group ◽  
Human Cancer Cell Lines ◽  
Ic50 Values

The compounds 2-amino-3-carboxamido-thieno[2,3-b]pyridines have demonstrated excellent anti-proliferative activity against human cancer cell lines, including the triple-negative breast cancer cell line MDA-MB-231. In this study, 81 novel thieno[2,3-b]pyridines were synthesised in four series to further improve their anti-proliferative activity, in particular by targeting an adjacent lipophilic pocket in the putative target enzyme phosphoinositide phospholipase C (PI-PLC). Overall, it was found that appending a propyl-aryl group at C-5 on 2-amino-3-carboxamido-thieno[2,3-b]pyridine resulted in compounds with potent biological activity, exhibiting IC50 values in the nanomolar range. The propyl linker could be an α,β-unsaturated ketone or a saturated propyl ketone, but the highest activity was obtained when allylic alcohols were the tether between thieno[2,3-b]pyridine and the appended aryl group, with compound 21r having IC50 values lower than 50 nM. Compounds with one extra carbon in the tether (i.e., a four-atom chain) were found to be considerably less active. Molecular modelling revealed this propyl tether places the newly introduced aryl ring in an untargeted lipophilic pocket within the active site of the phosphoinositide phospholipase C (PI-PLC) enzyme.

Mutation of Two Active-Site Residues Converts a Phosphatidylinositol-Specific Phospholipase C to a Glucose Phosphatase

2004 ◽  
Vol 126 (4) ◽  
pp. 1008-1009 ◽  
Author(s):  
Jianwen Feng ◽  
Kimberly Stieglitz ◽  
Mary F. Roberts
Keyword(s):  
Phospholipase C ◽  
Active Site ◽  
Active Site Residues

scholarly journals X-ray Structure of the R69D Phosphatidylinositol-Specific Phospholipase C Enzyme:  Insight into the Role of Calcium and Surrounding Amino Acids in Active Site Geometry and Catalysis

Biochemistry ◽  
2005 ◽  
Vol 44 (30) ◽  
pp. 9980-9989 ◽  
Author(s):  
David Apiyo ◽  
Li Zhao ◽  
Ming-Daw Tsai ◽  
Thomas L. Selby
Keyword(s):  
Amino Acids ◽  
Phospholipase C ◽  
Active Site ◽  
X Ray ◽  
Insight Into

Tryptophan 80 and Leucine 143 Are Critical for the Hydride Transfer Step of Thymidylate Synthase by Controlling Active Site Access†,‡

Biochemistry ◽  
2002 ◽  
Vol 41 (22) ◽  
pp. 7021-7029 ◽  
Author(s):  
Timothy A. Fritz ◽  
Lu Liu ◽  
Janet S. Finer-Moore ◽  
Robert M. Stroud
Keyword(s):  
Thymidylate Synthase ◽  
Active Site ◽  
Hydride Transfer ◽  
Transfer Step ◽  
Site Access
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