The substrate promiscuity of a phosphopantetheinyl transferase SchPPT for coenzyme A derivatives and acyl carrier proteins

2016 ◽  
Vol 198 (2) ◽  
pp. 193-197 ◽  
Author(s):  
Yue-Yue Wang ◽  
Hong-Dou Luo ◽  
Xiao-Sheng Zhang ◽  
Tao Lin ◽  
Hui Jiang ◽  
...  
Keyword(s):  
Coenzyme A ◽  
Phosphopantetheinyl Transferase ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins ◽  
Substrate Promiscuity

scholarly journals Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition

Science ◽  
2019 ◽  
Vol 363 (6426) ◽  
pp. eaau8959 ◽  
Author(s):  
Elaine Ballinger ◽  
John Mosior ◽  
Travis Hartman ◽  
Kristin Burns-Huang ◽  
Ben Gold ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Coenzyme A ◽  
Loss Of Function ◽  
Phosphopantetheinyl Transferase ◽  
Carrier Proteins ◽  
Regulatory Pathway ◽  
Acyl Carrier Proteins ◽  
Antimycobacterial Agents ◽  
Further Development ◽  
Cocrystal Structure

Mycobacterium tuberculosis (Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb’s cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4′-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT. Killing of Mtb by the compound is potentiated by another enzyme encoded in the same operon, Ppt hydrolase (PptH), that undoes the PptT reaction. Thus, loss-of-function mutants of PptH displayed antimicrobial resistance. Our PptT-inhibitor cocrystal structure may aid further development of antimycobacterial agents against this long-sought target. The opposing reactions of PptT and PptH uncover a regulatory pathway in CoA physiology.

scholarly journals Structure, function and dynamics in acyl carrier proteins

PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0219435 ◽  
Author(s):  
Rohit Farmer ◽  
Christopher Morton Thomas ◽  
Peter James Winn
Keyword(s):  
Structure Function ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins

scholarly journals Genetic construction and functional analysis of hybrid polyketide synthases containing heterologous acyl carrier proteins.

1993 ◽  
Vol 175 (8) ◽  
pp. 2197-2204 ◽  
Author(s):  
C Khosla ◽  
R McDaniel ◽  
S Ebert-Khosla ◽  
R Torres ◽  
D H Sherman ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Polyketide Synthases ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins

scholarly journals The effect of divalent cations on the thermostability of type II polyketide synthase acyl carrier proteins

AIChE Journal ◽  
2018 ◽  
Vol 64 (12) ◽  
pp. 4308-4318 ◽  
Author(s):  
Marco A. Rivas ◽  
Valentine C. Courouble ◽  
Miranda C. Baker ◽  
David L. Cookmeyer ◽  
Kristen E. Fiore ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Divalent Cations ◽  
Type Ii ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins

scholarly journals Evolutionary significance of self-acylation property in acyl carrier proteins

IUBMB Life ◽  
2009 ◽  
Vol 61 (8) ◽  
pp. 853-859 ◽  
Author(s):  
Ashish Misra ◽  
Namita Surolia ◽  
Avadhesha Surolia
Keyword(s):  
Evolutionary Significance ◽  
Carrier Proteins ◽  
Acyl Carrier Proteins
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