| Structural highlights
1r74 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Gene: | GNMT (Homo sapiens) |
| Activity: | Glycine N-methyltransferase, with EC number 2.1.1.20 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[GNMT_HUMAN] Defects in GNMT are the cause of glycine N-methyltransferase deficiency (GNMT deficiency) [MIM:606664]; also known as hypermethioninemia. The only clinical abnormalities in patients with this deficiency are mild hepatomegaly and chronic elevation of serum transaminases.
Function
[GNMT_HUMAN] Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.[1] [2]
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
Glycine N-methyltransferases (GNMTs) from three mammalian sources were compared with respect to their crystal structures and kinetic parameters. The crystal structure for the rat enzyme was published previously. Human and mouse GNMT were expressed in Escherichia coli in order to determine their crystal structures. Mouse GNMT was crystallized in two crystal forms, a monoclinic form and a tetragonal form. Comparison of the three structures reveals subtle differences, which may relate to the different kinetic properties of the enzymes.The flexible character of several loops surrounding the active site, along with an analysis of the active site boundaries, indicates that the observed conformations of human and mouse GNMTs are more open than that of the rat enzyme. There is an increase in kcat when going from rat to mouse to human, suggesting a correlation with the increased flexibility of some structural elements of the respective enzymes.
Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes.,Pakhomova S, Luka Z, Grohmann S, Wagner C, Newcomer ME Proteins. 2004 Nov 1;57(2):331-7. PMID:15340920[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pakhomova S, Luka Z, Grohmann S, Wagner C, Newcomer ME. Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes. Proteins. 2004 Nov 1;57(2):331-7. PMID:15340920 doi:10.1002/prot.20209
- ↑ Luka Z, Pakhomova S, Luka Y, Newcomer ME, Wagner C. Destabilization of human glycine N-methyltransferase by H176N mutation. Protein Sci. 2007 Sep;16(9):1957-64. Epub 2007 Jul 27. PMID:17660255 doi:10.1110/ps.072921507
- ↑ Pakhomova S, Luka Z, Grohmann S, Wagner C, Newcomer ME. Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes. Proteins. 2004 Nov 1;57(2):331-7. PMID:15340920 doi:10.1002/prot.20209
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