Oligomeric interactions maintain active-site structure in a non-cooperative enzyme family
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ABSTRACT:
SUBMITTER: John Francis Hunt
PROVIDER: EMPIAR-10872 | biostudies-other |
REPOSITORIES: biostudies-other
Publications
Oligomeric interactions maintain active-site structure in a noncooperative enzyme family.
Li Yaohui Y Zhang Rongzhen R Wang Chi C Forouhar Farhad F Clarke Oliver B OB Vorobiev Sergey S Singh Shikha S Montelione Gaetano T GT Szyperski Thomas T Xu Yan Y Hunt John F JF
The EMBO journal 20220708 17
The evolutionary benefit accounting for widespread conservation of oligomeric structures in proteins lacking evidence of intersubunit cooperativity remains unclear. Here, crystal and cryo-EM structures, and enzymological data, demonstrate that a conserved tetramer interface maintains the active-site structure in one such class of proteins, the short-chain dehydrogenase/reductase (SDR) superfamily. Phylogenetic comparisons support a significantly longer polypeptide being required to maintain an e ...[more]
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Project description:The evolutionary benefit accounting for widespread conservation of oligomeric structures in proteins lacking evidence of intersubunit cooperativity remains unclear. Here, crystal and cryo-EM structures as well as enzymological data demonstrate that a conserved tetramer interface maintains the active site structure in one such class of proteins, the short-chain dehydrogenase/reductase (SDR) superfamily. Phylogenetic comparisons support a significantly longer polypeptide being required to maintain an equivalent active site structure in the context of a single subunit. Oligomerization therefore enhances evolutionary fitness by reducing the metabolic cost of enzyme biosynthesis. The large surface area of the structure-stabilizing oligomeric interface yields a synergistic gain in fitness by increasing tolerance to activity-enhancing yet destabilizing mutations. We demonstrate that two paralogous SDR-superfamily enzymes with different specificities can form mixed heterotetramers that combine their individual enzymological properties. This suggests that oligomerization can also diversify the functions generated by a given metabolic investment, enhancing the fitness advantage provided by this architectural strategy.
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