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Wzb of Vibrio vulnificus represents a new group of low-molecular-weight protein tyrosine phosphatases with a unique insertion in the W-loop.

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Wang X, Ma Q
OpenAccess logo J Biol Chem 296 100280
Related entries: 7dhe, 7dhf

Cited: 4 times
EuropePMC logo PMID: 33450227

Abstract

Protein tyrosine phosphorylation regulates the production of capsular polysaccharide, an essential virulence factor of the deadly pathogen Vibrio vulnificus. The process requires the protein tyrosine kinase Wzc and its cognate phosphatase Wzb, both of which are largely uncharacterized. Herein, we report the structures of Wzb of V. vulnificus (VvWzb) in free and ligand-bound forms. VvWzb belongs to the low-molecular-weight protein tyrosine phosphatase (LMWPTP) family. Interestingly, it contains an extra four-residue insertion in the W-loop, distinct from all known LMWPTPs. The W-loop of VvWzb protrudes from the protein body in the free structure, but undergoes significant conformational changes to fold toward the active site upon ligand binding. Deleting the four-residue insertion from the W-loop severely impaired the enzymatic activity of VvWzb, indicating its importance for optimal catalysis. However, mutating individual residues or even substituting the whole insertion with four alanine residues only modestly decreased the enzymatic activity, suggesting that the contribution of the insertion to catalysis is not determined by the sequence specificity. Furthermore, inserting the four residues into Escherichia coli Wzb at the corresponding position enhanced its activity as well, indicating that the four-residue insertion in the W-loop can act as a general activity enhancing element for other LMWPTPs. The novel W-loop type and phylogenetic analysis suggested that VvWzb and its homologs should be classified into a new group of LMWPTPs. Our study sheds new insight into the catalytic mechanism and structural diversity of the LMWPTP family and promotes the understanding of the protein tyrosine phosphorylation system in prokaryotes.

Articles - 7dhd mentioned but not cited (1)

  1. Wzb of Vibrio vulnificus represents a new group of low-molecular-weight protein tyrosine phosphatases with a unique insertion in the W-loop. Wang X, Ma Q. J Biol Chem 296 100280 (2021)


Articles citing this publication (3)

  1. A structural exposé of noncanonical molecular reactivity within the protein tyrosine phosphatase WPD loop. Wang H, Perera L, Jork N, Zong G, Riley AM, Potter BVL, Jessen HJ, Shears SB. Nat Commun 13 2231 (2022)
  2. Structural basis for the recognition of the bacterial tyrosine kinase Wzc by its cognate tyrosine phosphatase Wzb. Alphonse S, Djemil I, Piserchio A, Ghose R. Proc Natl Acad Sci U S A 119 e2201800119 (2022)
  3. New biochemistry in the Rhodanese-phosphatase superfamily: emerging roles in diverse metabolic processes, nucleic acid modifications, and biological conflicts. Burroughs AM, Aravind L. NAR Genom Bioinform 5 lqad029 (2023)


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