5UNQ

Crystal Structure of Pt0534 Inactivated by 2-Oxo-3-pentynoate

Summary for 5UNQ

• Entry DOI: 10.2210/pdb5unq/pdb
• Descriptor: Putative tautomerase (3 entities in total)
• Functional Keywords: 4-oxalocrotonate tautomerase, mif, ciscaad, dehalogenase, hydrolase
• Biological source: Pusillimonas sp. (strain T7-7); More
• Total number of polymer chains: 6
• Total formula weight: 78808.17

Authors

LeVieux, J.,Baas, B.J.,Zhang, Y.J.,Whitman, C.P. (deposition date: 2017-01-31, release date: 2017-11-22, Last modification date: 2023-10-04)

Primary citation

Davidson, R.,Baas, B.J.,Akiva, E.,Holliday, G.L.,Polacco, B.J.,LeVieux, J.A.,Pullara, C.R.,Zhang, Y.J.,Whitman, C.P.,Babbitt, P.C.
A global view of structure-function relationships in the tautomerase superfamily.
J. Biol. Chem., 293:2342-2357, 2018

PubMed Abstract: The tautomerase superfamily (TSF) consists of more than 11,000 nonredundant sequences present throughout the biosphere. Characterized members have attracted much attention because of the unusual and key catalytic role of an N-terminal proline. These few characterized members catalyze a diverse range of chemical reactions, but the full scale of their chemical capabilities and biological functions remains unknown. To gain new insight into TSF structure-function relationships, we performed a global analysis of similarities across the entire superfamily and computed a sequence similarity network to guide classification into distinct subgroups. Our results indicate that TSF members are found in all domains of life, with most being present in bacteria. The eukaryotic members of the -3-chloroacrylic acid dehalogenase subgroup are limited to fungal species, whereas the macrophage migration inhibitory factor subgroup has wide eukaryotic representation (including mammals). Unexpectedly, we found that 346 TSF sequences lack Pro-1, of which 85% are present in the malonate semialdehyde decarboxylase subgroup. The computed network also enabled the identification of similarity paths, namely sequences that link functionally diverse subgroups and exhibit transitional structural features that may help explain reaction divergence. A structure-guided comparison of these linker proteins identified conserved transitions between them, and kinetic analysis paralleled these observations. Phylogenetic reconstruction of the linker set was consistent with these findings. Our results also suggest that contemporary TSF members may have evolved from a short 4-oxalocrotonate tautomerase-like ancestor followed by gene duplication and fusion. Our new linker-guided strategy can be used to enrich the discovery of sequence/structure/function transitions in other enzyme superfamilies.

PubMed: 29184004
DOI: 10.1074/jbc.M117.815340

Experimental method

X-RAY DIFFRACTION (1.976 Å)