| Structural highlights
Function
[RHMA_ECOLI] Catalyzes the reversible retro-aldol cleavage of 2-keto-3-deoxy-L-rhamnonate (KDR) to pyruvate and lactaldehyde. 2-keto-3-deoxy-L-mannonate, 2-keto-3-deoxy-L-lyxonate and 4-hydroxy-2-ketoheptane-1,7-dioate (HKHD) are also reasonably good substrates, although 2-keto-3-deoxy-L-rhamnonate is likely to be the physiological substrate.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
One of the major challenges in the postgenomic era is the functional assignment of proteins using sequence- and structure-based predictive methods coupled with experimental validation. We have used these approaches to investigate the structure and function of the Escherichia coli K-12 protein YfaU, annotated as a putative 4-hydroxy-2-ketoheptane-1,7-dioate aldolase (HpcH) in the sequence databases. HpcH is the final enzyme in the degradation pathway of the aromatic compound homoprotocatechuate. We have determined the crystal structure of apo-YfaU and the Mg (2+)-pyruvate product complex. Despite greater sequence and structural similarity to HpcH, genomic context suggests YfaU is instead a 2-keto-3-deoxy sugar aldolase like the homologous 2-dehydro-3-deoxygalactarate aldolase (DDGA). Enzyme kinetic measurements show activity with the probable physiological substrate 2-keto-3-deoxy- l-rhamnonate, supporting the functional assignment, as well as the structurally similar 2-keto-3-deoxy- l-mannonate and 2-keto-3-deoxy- l-lyxonate (see accompanying paper: Rakus, J. F., Fedorov, A. A., Fedorov, E. V., Glasner, M. E., Hubbard, B. K., Delli, J. D., Babbitt, P. C., Almo, S. C., and Gerlt, J. A. (2008) Biochemistry 47, XXXXX-XXXXX). YfaU has similar activity toward the HpcH substrate 4-hydroxy-2-ketoheptane-1,7-dioate and synthetic substrates 4-hydroxy-2-ketopentanoic acid and 4-hydroxy-2-ketohexanoic acid. This indicates a relaxed substrate specificity that complicates the functional assignment of members of this enzyme superfamily. Crystal structures suggest these enzymes use an Asp-His intersubunit dyad to activate a metal-bound water or hydroxide for proton transfer during catalysis.
Crystal Structure and Functional Assignment of YfaU, a Metal Ion Dependent Class II Aldolase from Escherichia coli K12.,Rea D, Hovington R, Rakus JF, Gerlt JA, Fulop V, Bugg TD, Roper DI Biochemistry. 2008 Aug 29. PMID:18754683[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rea D, Hovington R, Rakus JF, Gerlt JA, Fulop V, Bugg TD, Roper DI. Crystal Structure and Functional Assignment of YfaU, a Metal Ion Dependent Class II Aldolase from Escherichia coli K12. Biochemistry. 2008 Aug 29. PMID:18754683 doi:10.1021/bi800943g
- ↑ Rakus JF, Fedorov AA, Fedorov EV, Glasner ME, Hubbard BK, Delli JD, Babbitt PC, Almo SC, Gerlt JA. Evolution of enzymatic activities in the enolase superfamily: L-rhamnonate dehydratase. Biochemistry. 2008 Sep 23;47(38):9944-54. Epub 2008 Aug 29. PMID:18754693 doi:10.1021/bi800914r
- ↑ Rea D, Hovington R, Rakus JF, Gerlt JA, Fulop V, Bugg TD, Roper DI. Crystal Structure and Functional Assignment of YfaU, a Metal Ion Dependent Class II Aldolase from Escherichia coli K12. Biochemistry. 2008 Aug 29. PMID:18754683 doi:10.1021/bi800943g
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