| Structural highlights
Function
SYWC_HUMAN Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Higher eukaryote tRNA synthetases have expanded functions that come from enlarged, more differentiated structures that were adapted to fit aminoacylation function. How those adaptations affect catalytic mechanisms is not known. Presented here is the structure of a catalytically active natural splice variant of human tryptophanyl-tRNA synthetase (TrpRS) that is a potent angiostatic factor. This and related structures suggest that a eukaryote-specific N-terminal extension of the core enzyme changed substrate recognition by forming an active site cap. At the junction of the extension and core catalytic unit, an arginine is recruited to replace a missing landmark lysine almost 200 residues away. Mutagenesis, rapid kinetic, and substrate binding studies support the functional significance of the cap and arginine recruitment. Thus, the enzyme function of human TrpRS has switched more to the N terminus of the sequence. This switch has the effect of creating selective pressure to retain the N-terminal extension for functional expansion.
Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase.,Yang XL, Guo M, Kapoor M, Ewalt KL, Otero FJ, Skene RJ, McRee DE, Schimmel P Structure. 2007 Jul;15(7):793-805. PMID:17637340[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wakasugi K, Slike BM, Hood J, Otani A, Ewalt KL, Friedlander M, Cheresh DA, Schimmel P. A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):173-7. Epub 2002 Jan 2. PMID:11773626 doi:10.1073/pnas.012602099
- ↑ Bange FC, Flohr T, Buwitt U, Bottger EC. An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase. FEBS Lett. 1992 Mar 30;300(2):162-6. PMID:1373391
- ↑ Otani A, Slike BM, Dorrell MI, Hood J, Kinder K, Ewalt KL, Cheresh D, Schimmel P, Friedlander M. A fragment of human TrpRS as a potent antagonist of ocular angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):178-83. Epub 2002 Jan 2. PMID:11773625 doi:10.1073/pnas.012601899
- ↑ Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P. Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14903-7. Epub 2003 Nov 20. PMID:14630953 doi:10.1073/pnas.2436330100
- ↑ Yang XL, Guo M, Kapoor M, Ewalt KL, Otero FJ, Skene RJ, McRee DE, Schimmel P. Functional and crystal structure analysis of active site adaptations of a potent anti-angiogenic human tRNA synthetase. Structure. 2007 Jul;15(7):793-805. PMID:17637340 doi:10.1016/j.str.2007.05.009
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