Structural insights into the inhibition properties of archaeon citrate synthase from Metallosphaera sedula

PloS One
Seul Hoo LeeKyung-Jin Kim

Abstract

Metallosphaera sedula is a thermoacidophilic archaeon and has an incomplete TCA/glyoxylate cycle that is used for production of biosynthetic precursors of essential metabolites. Citrate synthase from M. sedula (MsCS) is an enzyme involved in the first step of the incomplete TCA/glyoxylate cycle by converting oxaloacetate and acetyl-CoA into citrate and coenzyme A. To elucidate the inhibition properties of MsCS, we determined its crystal structure at 1.7 Å resolution. Like other Type-I CS, MsCS functions as a dimer and each monomer consists of two distinct domains, a large domain and a small domain. The oxaloacetate binding site locates at the cleft between the two domains, and the active site was more closed upon binding of the oxaloacetate substrate than binding of the citrate product. Interestingly, the inhibition kinetic analysis showed that, unlike other Type-I CSs, MsCS is non-competitively inhibited by NADH. Finally, amino acids and structural comparison of MsCS with other Type-II CSs, which were reported to be non-competitively inhibited by NADH, revealed that MsCS has quite unique NADH binding mode for non-competitive inhibition.

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Citations

Feb 19, 2021·Journal of Agricultural and Food Chemistry·Seul Hoo LeeKyung-Jin Kim

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Methods Mentioned

BETA
PCR
size-exclusion chromatography
PISA

Software Mentioned

HKL2000
DynDom
Origin
WinCoot REFMAC5
PISA
MOLREP
CCP4

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