Universality of critical active site glutamate as an acid-base catalyst in serine hydroxymethyltransferase function.

ABSTRACT: Serine hydroxymethyltransferase (SHMT) is a key enzyme in the one-carbon metabolic pathway, utilizing the vitamin B₆ derivative pyridoxal 5'-phosphate (PLP) and vitamin B₉ derivative tetrahydrofolate (THF) coenzymes to produce essential biomolecules. Many types of cancer utilize SHMT in metabolic reprogramming, exposing the enzyme as a compelling target for antimetabolite chemotherapies. In pursuit of elucidating the catalytic mechanism of SHMT to aid in the design of SHMT-specific inhibitors, we have used room-temperature neutron crystallography to directly determine the protonation states in a model enzyme Thermus thermophilus SHMT (TthSHMT), which exhibits a conserved active site compared to human mitochondrial SHMT2 (hSHMT2). Here we report the analy

SUBMITTER: Drago VN 

PROVIDER: S-EPMC11323337 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature