Sandbox Wabash 24 Fumarase

When studying fumarase 2 sites were identified to potentially be the active site. The first site (A-site) binds inhibitors (citrate, and pyromellitic acid) and is made up of parts of 3 of the 4 subunits that comprise fumarase. The second site (B-site) binds L-malate and is made up by parts of 1 of the 4 subunits. The A-site is located deeper within the enzyme complex and bound water that interacted with H188 whereas the B-site exists closer to the surface and the only basic group it binds is H129. ^[1]. In order to differentiate between the sites to determine the true binding site scientists compared whether changing Histidine 129 or Histidine 188 impacted the complex. Histidine was picked because previous research demonstrated that histidine was participating in catalysis. The researchers then inserted mutations and determined that the A-site was the active site based on mutation results and crystal structures.

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Disease

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Structural highlights

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