Mechanism
The bridging water or hydroxide ligand acts as a nucleophile during the hydrolysis reaction, but the exact mechanism of catalysis is not yet known. The catalytic mechanisms of hydrolase enzymes depend greatly on the identity of the bridging ligand, which can be challenging to determine due to the difficulty of studying hydrogen atoms via x-ray crystallography.
The histidine residues shown in the mechanism to the right, H178 and H79, are conserved in all MetAPs (MetAP1s and MetAP2s) sequenced to date, suggesting their presence is important to catalytic activity. Based upon X-ray crystallographic data, histidine 79 (H79) has been proposed to help position the methionine residue in the active site and transfer a proton to the newly exposed N-terminal amine. Lowther and Colleagues have proposed two possible mechanisms for MetAP2 in E. coli, shown at the right.
Read more about this topic: METAP2
Famous quotes containing the word mechanism:
“When one of us dies of cancer, loses her mind, or commits suicide, we must not blame her for her inability to survive an ongoing political mechanism bent on the destruction of that human being. Sanity remains defined simply by the ability to cope with insane conditions.”
—Ana Castillo (b. 1953)
“Life is an offensive, directed against the repetitious mechanism of the Universe.”
—Alfred North Whitehead (1861–1947)
“A mechanism of some kind stands between us and almost every act of our lives.”
—Sarah Patton Boyle, U.S. civil rights activist and author. The Desegregated Heart, part 3, ch. 2 (1962)