Methionine adenosyltransferase: Difference between revisions
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MAT consists of α and β subunits. The MATα1 and <scene name='90/907472/Mat2a/4'>MATα2</scene> subunits are catalytic subunits while MATβ is a regulatory subunit. MATα2 subunits can form <scene name='49/493038/Tetramer/1'>tetramers</scene>, where the active site is found <scene name='49/493038/Tetramer/2'>between two of the subunits</scene>. The subunits are encoded on different genes in humans, so they are created separately and can then come together to form various complexes, such as MATαβ or MATα2 dimers <ref name="Murray et al." />. Not much is currently known about the function of this regulatory subunit and how it regulates the function of the enzyme<ref>DOI:10.1107/S2052252514012585</ref>. However, Murray et al.<ref name="Murray et al." /> show that even in the absence of the regulatory subunit, the active site found in the catalytic subunit remains functional. | MAT consists of α and β subunits. The MATα1 and <scene name='90/907472/Mat2a/4'>MATα2</scene> subunits are catalytic subunits while MATβ is a regulatory subunit. MATα2 subunits can form <scene name='49/493038/Tetramer/1'>tetramers</scene>, where the active site is found <scene name='49/493038/Tetramer/2'>between two of the subunits</scene>. The subunits are encoded on different genes in humans, so they are created separately and can then come together to form various complexes, such as MATαβ or MATα2 dimers <ref name="Murray et al." />. Not much is currently known about the function of this regulatory subunit and how it regulates the function of the enzyme<ref>DOI:10.1107/S2052252514012585</ref>. However, Murray et al.<ref name="Murray et al." /> show that even in the absence of the regulatory subunit, the active site found in the catalytic subunit remains functional. | ||
The biological assembly of rat S-adenosylmethionine synthetase is a <scene name='49/493038/Cv/ | The biological assembly of rat S-adenosylmethionine synthetase is a <scene name='49/493038/Cv/11'>homotetramer</scene>. The <scene name='49/493038/Cv/10'>active site of MAT is located between adjacent subunits</scene><ref>PMID:12888348</ref>. The <scene name='49/493038/Substrates/4'>substrates</scene> used by the enzyme are methionine and ATP. Notably, ATP is not used as a source of energy in this reaction like it is for many other processes. Instead, it is used as a substrate in the synthesis reaction. Methionine and ATP enter the active site and are stabilized by residues present there, including lysine and histidine. Once the reaction begins to take place, methionine flips toward the 5' carbon of the adenosine sugar<ref>doi:10.1042/BJ20121580</ref>. Following nucleophilic attack of the sulfur on the carbon, the C-O bond between the phosphates and the carbon breaks, and the <scene name='49/493038/Product/4'>products</scene> are formed (tripolyphosphate not pictured). SAM is released from the active site first. MAT also catalyzes hydrolysis of the tripolyphosphate into pyrophosphate and orthophosphate, which are then released from the active site <ref>Niland CN, Ghosh A, Cahill SM, Schramm VL. Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. ACS Biochemistry. 2021 Mar 3;60 (10) 791-801. doi: https://doi.org/10.1021/acs.biochem.0c00998</ref>. | ||
== Gating Loop == | == Gating Loop == | ||
