Structural highlights
7lnn is a 2 chain structure with sequence from Escherichia coli 908573. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Gene: | metK, HMPREF1611_00479 (Escherichia coli 908573) |
| Activity: | Methionine adenosyltransferase, with EC number 2.5.1.6 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[V0ZE41_ECOLX] Catalyzes the formation of S-adenosylmethionine (AdoMet) from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme.[HAMAP-Rule:MF_00086]
Publication Abstract from PubMed
Protein conformational changes can facilitate the binding of noncognate substrates and underlying promiscuous activities. However, the contribution of substrate conformational dynamics to this process is comparatively poorly understood. Here, we analyze human (hMAT2A) and Escherichia coli (eMAT) methionine adenosyltransferases that have identical active sites but different substrate specificity. In the promiscuous hMAT2A, noncognate substrates bind in a stable conformation to allow catalysis. In contrast, noncognate substrates sample stable productive binding modes less frequently in eMAT owing to altered mobility in the enzyme active site. Different cellular concentrations of substrates likely drove the evolutionary divergence of substrate specificity in these orthologues. The observation of catalytic promiscuity in hMAT2A led to the detection of a new human metabolite, methyl thioguanosine, that is produced at elevated levels in a cancer cell line. This work establishes that identical active sites can result in different substrate specificity owing to the effects of substrate and enzyme dynamics.
Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases.,Gade M, Tan LL, Damry AM, Sandhu M, Brock JS, Delaney A, Villar-Briones A, Jackson CJ, Laurino P JACS Au. 2021 Nov 19;1(12):2349-2360. doi: 10.1021/jacsau.1c00464. eCollection, 2021 Dec 27. PMID:34977903[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gade M, Tan LL, Damry AM, Sandhu M, Brock JS, Delaney A, Villar-Briones A, Jackson CJ, Laurino P. Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases. JACS Au. 2021 Nov 19;1(12):2349-2360. doi: 10.1021/jacsau.1c00464. eCollection, 2021 Dec 27. PMID:34977903 doi:http://dx.doi.org/10.1021/jacsau.1c00464
