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The crystal structure of D-threonine aldolase from Alcaligenes xylosoxidans provides insight into a metal ion assisted PLP-dependent mechanism.

Uhl MK, Oberdorfer G, Steinkellner G, Riegler-Berket L, Mink D, van Assema F, Schürmann M, Gruber K
PLoS One 10 e0124056 (2015)
Cited: 9 times
EuropePMC logo PMID: 25884707

Abstract

Threonine aldolases catalyze the pyridoxal phosphate (PLP) dependent cleavage of threonine into glycine and acetaldehyde and play a major role in the degradation of this amino acid. In nature, L- as well as D-specific enzymes have been identified, but the exact physiological function of D-threonine aldolases (DTAs) is still largely unknown. Both types of enantio-complementary enzymes have a considerable potential in biocatalysis for the stereospecific synthesis of various β-hydroxy amino acids, which are valuable building blocks for the production of pharmaceuticals. While several structures of L-threonine aldolases (LTAs) have already been determined, no structure of a DTA is available to date. Here, we report on the determination of the crystal structure of the DTA from Alcaligenes xylosoxidans (AxDTA) at 1.5 Å resolution. Our results underline the close relationship of DTAs and alanine racemases and allow the identification of a metal binding site close to the PLP-cofactor in the active site of the enzyme which is consistent with the previous observation that divalent cations are essential for DTA activity. Modeling of AxDTA substrate complexes provides a rationale for this metal dependence and indicates that binding of the β-hydroxy group of the substrate to the metal ion very likely activates this group and facilitates its deprotonation by His193. An equivalent involvement of a metal ion has been implicated in the mechanism of a serine dehydratase, which harbors a metal ion binding site in the vicinity of the PLP cofactor at the same position as in DTA. The structure of AxDTA is completely different to available structures of LTAs. The enantio-complementarity of DTAs and LTAs can be explained by an approximate mirror symmetry of crucial active site residues relative to the PLP-cofactor.

Reviews - 4v15 mentioned but not cited (1)

  1. Threonine aldolases: perspectives in engineering and screening the enzymes with enhanced substrate and stereo specificities. Fesko K. Appl Microbiol Biotechnol 100 2579-2590 (2016)

Articles - 4v15 mentioned but not cited (2)

  1. Structure-Aware Mycobacterium tuberculosis Functional Annotation Uncloaks Resistance, Metabolic, and Virulence Genes. Modlin SJ, Elghraoui A, Gunasekaran D, Zlotnicki AM, Dillon NA, Dhillon N, Kuo N, Robinhold C, Chan CK, Baughn AD, Valafar F. mSystems 6 e0067321 (2021)
  2. Crystallization and X-ray analysis of D-threonine aldolase from Chlamydomonas reinhardtii. Hirato Y, Goto M, Tokuhisa M, Tanigawa M, Nishimura K. Acta Crystallogr F Struct Biol Commun 73 86-89 (2017)


Reviews citing this publication (3)

  1. Current Advances on Structure-Function Relationships of Pyridoxal 5'-Phosphate-Dependent Enzymes. Liang J, Han Q, Tan Y, Ding H, Li J. Front Mol Biosci 6 4 (2019)
  2. Enzymatic asymmetric synthesis of chiral amino acids. Xue YP, Cao CH, Zheng YG. Chem Soc Rev 47 1516-1561 (2018)
  3. Enzymes useful for chiral compound synthesis: structural biology, directed evolution, and protein engineering for industrial use. Kataoka M, Miyakawa T, Shimizu S, Tanokura M. Appl Microbiol Biotechnol 100 5747-5757 (2016)

Articles citing this publication (3)

  1. Marine Proteobacteria metabolize glycolate via the β-hydroxyaspartate cycle. Schada von Borzyskowski L, Severi F, Krüger K, Hermann L, Gilardet A, Sippel F, Pommerenke B, Claus P, Cortina NS, Glatter T, Zauner S, Zarzycki J, Fuchs BM, Bremer E, Maier UG, Amann RI, Erb TJ. Nature 575 500-504 (2019)
  2. Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1'-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators. McCune CD, Beio ML, Sturdivant JM, de la Salud-Bea R, Darnell BM, Berkowitz DB. J Am Chem Soc 139 14077-14089 (2017)
  3. Structure of pyridoxal 5'-phosphate-bound D-threonine aldolase from Chlamydomonas reinhardtii. Hirato Y, Goto M, Mizobuchi T, Muramatsu H, Tanigawa M, Nishimura K. Acta Crystallogr F Struct Biol Commun 79 31-37 (2023)


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