Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A tripartite fusion construct encoding the amino-terminal half of EcoRI endonuclease followed by amino acids 217-299 of the filamentous bacteriophage gene I protein (pI) attached to the enzymatic portion of alkaline phosphatase results in the production of two proteins. The larger protein, pIf, is the complete tripartite fusion protein while the smaller protein, pIf*, results from internal initiation of translation at pI methionine 241. Both pIf and pIf* span the Escherichia coli inner membrane via a 20-amino-acid hydrophobic stretch of pI with their amino termini in the cytoplasm and their carboxyl-terminal alkaline phosphatase domains in the periplasm. The alkaline phosphatase moiety of approximately 70% of pIf is released into the periplasm by in vivo proteolysis, but only about 10% of pIf* is cleaved. Neither DegP, OmpT, nor protease III are responsible for the cleavage in vivo, and leader peptidase is unable to cleave the fusion protein in vitro. Deletion and substitution analyses demonstrate that the degree of periplasmic cleavage depends on the sequence of the cytoplasmic domain of the fusion proteins. Possible mechanisms for this transmembrane-directed cleavage event are compared to proposed models for signal transduction.
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PMID:The membrane domain of a bacteriophage assembly protein. Transmembrane-directed proteolysis of a membrane-spanning fusion protein. 844 11

Recently determined X-ray crystal structures of moonlighting proteins are helping to elucidate how a protein can evolve two different functions and, in some cases, switch between its two functions in response to cellular conditions. X-ray crystal structures of the I-AniI homing endonuclease/maturase and the PutA proline dehydrogenase/transcription factor have provided evidence that these proteins utilize separate protein surfaces for their multiple functions. Also, the structure of the DegP (HtrA) protease/chaperone has revealed information about the mechanism of its chaperone activity and suggests how the protein regulates its protease activity. Comparing the structure of eta-crystallin/retinal dehydrogenase with structures of its single-function enzyme homologs provides clues to changes in the protein structure that may have improved its ability to serve as a crystallin, but at the same time may have adversely affected its catalytic activity.
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PMID:Molecular mechanisms for multitasking: recent crystal structures of moonlighting proteins. 1558 89