N-terminal acetylome analysis reveals the specificity of Naa50 (Nat5) and suggests a kinetic competition between N-terminal acetyltransferases and methionine aminopeptidases

PROTEOMICS ◽  
2015 ◽  
Vol 15 (14) ◽  
pp. 2436-2446 ◽  
Author(s):  
Petra Van Damme ◽  
Kristine Hole ◽  
Kris Gevaert ◽  
Thomas Arnesen
Keyword(s):  
Methionine Aminopeptidases

Discovery of natural product ovalicin sensitive type 1 methionine aminopeptidases: molecular and structural basis

2019 ◽  
Vol 476 (6) ◽  
pp. 991-1003 ◽  
Author(s):  
Vijaykumar Pillalamarri ◽  
Tarun Arya ◽  
Neshatul Haque ◽  
Sandeep Chowdary Bala ◽  
Anil Kumar Marapaka ◽  
...  
Keyword(s):  
Natural Product ◽  
Active Site ◽  
Covalent Modification ◽  
Structural Basis ◽  
Wild Type ◽  
Methionine Aminopeptidases ◽  
Synthetic Derivative ◽  
Dynamics Simulations

Abstract Natural product ovalicin and its synthetic derivative TNP-470 have been extensively studied for their antiangiogenic property, and the later reached phase 3 clinical trials. They covalently modify the conserved histidine in Type 2 methionine aminopeptidases (MetAPs) at nanomolar concentrations. Even though a similar mechanism is possible in Type 1 human MetAP, it is inhibited only at millimolar concentration. In this study, we have discovered two Type 1 wild-type MetAPs (Streptococcus pneumoniae and Enterococcus faecalis) that are inhibited at low micromolar to nanomolar concentrations and established the molecular mechanism. F309 in the active site of Type 1 human MetAP (HsMetAP1b) seems to be the key to the resistance, while newly identified ovalicin sensitive Type 1 MetAPs have a methionine or isoleucine at this position. Type 2 human MetAP (HsMetAP2) also has isoleucine (I338) in the analogous position. Ovalicin inhibited F309M and F309I mutants of human MetAP1b at low micromolar concentration. Molecular dynamics simulations suggest that ovalicin is not stably placed in the active site of wild-type MetAP1b before the covalent modification. In the case of F309M mutant and human Type 2 MetAP, molecule spends more time in the active site providing time for covalent modification.

Characterization of clioquinol and analogues as novel inhibitors of methionine aminopeptidases from Mycobacterium tuberculosis

Tuberculosis ◽  
2011 ◽  
Vol 91 ◽  
pp. S61-S65 ◽  
Author(s):  
Omonike Olaleye ◽  
Tirumalai R. Raghunand ◽  
Shridhar Bhat ◽  
Curtis Chong ◽  
Peihua Gu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Methionine Aminopeptidases

Identification of Pyridinylpyrimidines as Inhibitors of Human Methionine Aminopeptidases

2006 ◽  
Vol 118 (23) ◽  
pp. 3856-3859 ◽  
Author(s):  
Xiaoyi Hu ◽  
Anthony Addlagatta ◽  
Brian W. Matthews ◽  
Jun O. Liu
Keyword(s):  
Methionine Aminopeptidases

Kinetic and Mutational Studies of the Number of Interacting Divalent Cations Required by Bacterial and Human Methionine Aminopeptidases†

Biochemistry ◽  
2007 ◽  
Vol 46 (44) ◽  
pp. 12833-12843 ◽  
Author(s):  
Xiaoyi V. Hu ◽  
Xiaochun Chen ◽  
Kee Chung Han ◽  
Albert S. Mildvan ◽  
Jun O. Liu
Keyword(s):  
Divalent Cations ◽  
Methionine Aminopeptidases

scholarly journals Mutations at the S1 Sites of Methionine Aminopeptidases fromEscherichia coliandHomo sapiensReveal the Residues Critical for Substrate Specificity

2004 ◽  
Vol 279 (20) ◽  
pp. 21128-21134 ◽  
Author(s):  
Jing-Ya Li ◽  
Yong-Mei Cui ◽  
Ling-Ling Chen ◽  
Min Gu ◽  
Jia Li ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Methionine Aminopeptidases

Methionine aminopeptidases type I and type II are essential to control cell proliferation

2005 ◽  
Vol 95 (6) ◽  
pp. 1191-1203 ◽  
Author(s):  
Sylvie G. Bernier ◽  
Nazbeh Taghizadeh ◽  
Charles D. Thompson ◽  
William F. Westlin ◽  
Gerhard Hannig
Keyword(s):  
Cell Proliferation ◽  
Control Cell ◽  
Type I ◽  
Type Ii ◽  
Methionine Aminopeptidases
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