1w37
2-KETO-3-DEOXYGLUCONATE(KDG) ALDOLASE OF SULFOLOBUS SOLFATARICUS
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OverviewOverview
The hyperthermophilic Archaea Sulfolobus solfataricus grows optimally, above 80 degrees C and metabolizes glucose by a non-phosphorylative, variant of the Entner-Doudoroff pathway. In this pathway glucose, dehydrogenase and gluconate dehydratase catalyze the oxidation of glucose, to gluconate and the subsequent dehydration of gluconate to, D-2-keto-3-deoxygluconate (KDG). KDG aldolase (KDGA) then catalyzes the, cleavage of KDG to D-glyceraldehyde and pyruvate. It has recently been, shown that all the enzymes of this pathway exhibit a catalytic promiscuity, that also enables them to be used for the metabolism of galactose. This, phenomenon, known as metabolic pathway promiscuity, depends crucially on, the ability of KDGA to cleave KDG and D-2-keto-3-deoxygalactonate (KDGal), in both cases producing pyruvate and D-glyceraldehyde. In turn, the, aldolase exhibits a remarkable lack of stereoselectivity in the, condensation reaction of pyruvate and D-glyceraldehyde, forming a mixture, of KDG and KDGal. We now report the structure of KDGA, determined by, multiwavelength anomalous diffraction phasing, and confirm that it is a, member of the tetrameric N-acetylneuraminate lyase superfamily of Schiff, base-forming aldolases. Furthermore, by soaking crystals of the aldolase, at more than 80 degrees C below its temperature activity optimum, we have, been able to trap Schiff base complexes of the natural substrates, pyruvate, KDG, KDGal, and pyruvate plus D-glyceraldehyde, which have, allowed rationalization of the structural basis of promiscuous substrate, recognition and catalysis. It is proposed that the active site of the, enzyme is rigid to keep its thermostability but incorporates extra, functionality to be promiscuous.
About this StructureAbout this Structure
1W37 is a Single protein structure of sequence from Sulfolobus solfataricus with NA and GOL as ligands. Active as 2-dehydro-3-deoxyglucarate aldolase, with EC number 4.1.2.20 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
The structural basis for substrate promiscuity in 2-keto-3-deoxygluconate aldolase from the Entner-Doudoroff pathway in Sulfolobus solfataricus., Theodossis A, Walden H, Westwick EJ, Connaris H, Lamble HJ, Hough DW, Danson MJ, Taylor GL, J Biol Chem. 2004 Oct 15;279(42):43886-92. Epub 2004 Jul 20. PMID:15265860
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