Structural highlights
4uxd is a 4 chain structure with sequence from Picrophilus torridus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.5Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
KDGA_PICTO Involved in the degradation of glucose via the Entner-Doudoroff pathway. Catalyzes the reversible cleavage of 2-keto-3-deoxy-6-phosphogluconate (KDPG) and 2-keto-3-deoxygluconate (KDG) forming pyruvate and glyceraldehyde 3-phosphate or glyceraldehyde, respectively. It is also able to catalyze the reversible cleavage of 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) and 2-keto-3-deoxygalactonate (KDGal). It is equally active with both D- and L-glyceraldehyde.[1]
Publication Abstract from PubMed
The thermoacidophilic archaea Picrophilus torridus and Sulfolobus solfataricus catabolize glucose via a nonphosphorylative Entner-Doudoroff pathway and a branched Entner-Doudoroff pathway, respectively. Key enzymes for these Entner-Doudoroff pathways are the aldolases, 2-keto-3-deoxygluconate aldolase (KDG-aldolase) and 2-keto-3-deoxy-6-phosphogluconate aldolase [KD(P)G-aldolase]. KDG-aldolase from P. torridus (Pt-KDG-aldolase) is highly specific for the nonphosphorylated substrate, 2-keto-3-deoxygluconate (KDG), whereas KD(P)G-aldolase from S. solfataricus [Ss-KD(P)G-aldolase] is an enzyme that catalyzes the cleavage of both KDG and 2-keto-3-deoxy-6-phosphogluconate (KDPG), with a preference for KDPG. The structural basis for the high specificity of Pt-KDG-aldolase for KDG as compared to the more promiscuous Ss-KD(P)G-aldolase has not been analyzed before. In this work, we report the elucidation of the structure of Ss-KD(P)G-aldolase in complex with KDPG at 2.35 A and that of KDG-aldolase from P. torridus at 2.50 A resolution. By superimposition of the active sites of the two enzymes, and subsequent site-directed mutagenesis studies, a network of four amino acids, namely, Arg106, Tyr132, Arg237, and Ser241, was identified in Ss-KD(P)G-aldolase that interact with the negatively charged phosphate group of KDPG, thereby increasing the affinity of the enzyme for KDPG. This KDPG-binding network is absent in Pt-KDG-aldolase, which explains the low catalytic efficiency of KDPG cleavage.
Insights into the Substrate Specificity of Archaeal Entner-Doudoroff Aldolases: The Structures of Picrophilus torridus 2-Keto-3-deoxygluconate Aldolase and Sulfolobus solfataricus 2-Keto-3-deoxy-6-phosphogluconate Aldolase in Complex with 2-Keto-3-deoxy-6-phosphogluconate.,Zaitsev V, Johnsen U, Reher M, Ortjohann M, Taylor GL, Danson MJ, Schonheit P, Crennell SJ Biochemistry. 2018 Jun 13. doi: 10.1021/acs.biochem.8b00535. PMID:29812914[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Reher M, Fuhrer T, Bott M, Schonheit P. The nonphosphorylative Entner-Doudoroff pathway in the thermoacidophilic euryarchaeon Picrophilus torridus involves a novel 2-keto-3-deoxygluconate- specific aldolase. J Bacteriol. 2010 Feb;192(4):964-74. doi: 10.1128/JB.01281-09. Epub 2009 Dec 18. PMID:20023024 doi:http://dx.doi.org/10.1128/JB.01281-09
- ↑ Zaitsev V, Johnsen U, Reher M, Ortjohann M, Taylor GL, Danson MJ, Schonheit P, Crennell SJ. Insights into the Substrate Specificity of Archaeal Entner-Doudoroff Aldolases: The Structures of Picrophilus torridus 2-Keto-3-deoxygluconate Aldolase and Sulfolobus solfataricus 2-Keto-3-deoxy-6-phosphogluconate Aldolase in Complex with 2-Keto-3-deoxy-6-phosphogluconate. Biochemistry. 2018 Jun 13. doi: 10.1021/acs.biochem.8b00535. PMID:29812914 doi:http://dx.doi.org/10.1021/acs.biochem.8b00535
