N-Terminal nucleophile hydrolases

Threonine peptidases (and some cysteine and serine peptidases) have only one active site residue, which is the N-terminus of the mature protein. Such a peptidase is known as an N-terminal nucleophile hydrolase or Ntn-hydrolase. The amino group of the N-terminal residue performs the role of the general base. The catalytic subunits of the proteasome are examples of Ntn-hydrolases. 

As anticipated from their sequence similarity, the (non-catalytic) a- and the (catalytic) P-type subunits have the same fold (Lowe et al. 1995 Groll et al. 1997) a four-layer a+p structure with two antiparallel five-stranded P sheets, flanked on one side by two, on the other side by three a helices. In the P-type subunits, the P-sheet sandwich is closed at one end by four hairpin loops and open at the opposite end to form the active-site cleft the cleft is oriented towards the inner surface of the central cavity. In the a-type subunits an additional helix formed by an N-terminal extension crosses the top of the P-sheet sandwich and fills this cleft. Initially, the proteasome fold was believed to be unique however it turned out to be prototypical of a new superfamily of proteins referred to as Ntn (N-terminal nucleophile) hydrolases (Brannigan et al. 1995). 

N-Terminal nucleophile hydrolases autoactivation of 621 Termites, protozoa in 19 Tertiary structure of a protein 59 TES buffer 99... 

Glutamine is one of the principal combined forms of ammonia that is transported throughout the body (Chapter 24). Glucosamine 6-phosphate synthase, which catalyzes the reaction of Eq. 20-5, is an amido-transferase of the N-terminal nucleophile hydrolase superfamily (Chapter 12).31 It hydrolyzes the amide... 

The structure of the 20S proteasome (Fig. 2.13) from Thermoplasma acidophilum displays four rings stacked upon each other surrounding a central cavity in which proteolysis takes place. An N-terminal threonine has been identified as an essential active site residue of the protease center. The OH-group of the threonine functions as a nucleophile during hydrolysis of the petide bond. A similar mechanism of hydrolysis has been shown for other hydrolases, which, because of this property, are now included in the family of N-terminal nucleophile hydrolases. For some /1-subunits of eucaryotes the N-terminal threonine is generated by autoproteolysis of an N-terminal prosequence. 

A. Lodola, D. Branduardi, M. De Vivo, L. Capoferri, M. Mor, D. Piomelli, and A. Cavalli, PLoS One, 7(2), c32397 (2012). A Catalytic Mechanism for Cysteine N-Terminal Nucleophile Hydrolases, as Revealed by Free Energy Simulations. 

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