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Review
. 2013 Jan;44(1):129-42.
doi: 10.1007/s00726-011-1209-3. Epub 2012 Mar 10.

γ-Glutamylamines and neurodegenerative diseases

Thomas M Jeitner  1 , Kevin Battaile, Arthur J L Cooper
Affiliations
Review

γ-Glutamylamines and neurodegenerative diseases

Thomas M Jeitner et al. Amino Acids. 2013 Jan.

Abstract

Transglutaminases catalyze the formation of γ-glutamylamines utilizing glutamyl residues and amine-bearing compounds such as lysyl residues and polyamines. These γ-glutamylamines can be released from proteins by proteases in an intact form. The free γ-glutamylamines can be catabolized to 5-oxo-L-proline and the free amine by γ-glutamylamine cyclotransferase. Free γ-glutamylamines, however, accumulate in the CSF and affected areas of Huntington Disease brain. This observation suggests transglutaminase-derived γ-glutamylamines may play a more significant role in neurodegeneration than previously thought. The following monograph reviews the metabolism of γ-glutamylamines and examines the possibility that these species contribute to neurodegeneration.

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Figures

Figure 1
Figure 1. γ-Glutamylamines
The structures for the free and protein-bound forms of glutamate and some γ-glutamylamines are shown in the upper and lower panels, respectively.
Figure 2
Figure 2. Structure of Transglutaminase 2
The upper illustrations represent the closed (A) and open (B) conformations of transglutaminase 2 as well as the merger of these conformations (C). The lower diagram shows a ribbon diagram of the active site with γ-glutamyl-ε-lysine in place (D). These figures were generated using the program CCP4MG from the PDB coordinates IKV3 (blue) and ZQ3Z (magenta) (McNicholas et al. 2011).
Figure 3
Figure 3. Transamidation as catalyzed by Transglutaminases
Adapted from IIsmaa et al. (2003).
Figure 4
Figure 4. Structural Features of γ-Glutamylamine Cyclotransferase
The enzyme complexed with pyroglutamic acid is shown in A with the relative position of the active site reside in the absence (magenta) and presence (blue) represented in B. Part C depicts the details in B oriented at 180 degrees around the x axis. These figures were generated using the program CCP4MG from the PDB coordinates 3JUB (magenta) and 3JUC (blue) (McNicholas et al. 2011).
Figure 5
Figure 5. Catalytic mechanism of γ-glutamylamine cyclotransferase
Adapted from Oakley et al. (2010).
See this image and copyright information in PMC

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