The rhodanese/Cdc25 phosphatase superfamily. Sequence-structure-function relations.
Rhodanese domains are ubiquitous structural modules occurring in the three major evolutionary phyla. They are found as tandem repeats, with the C-terminal domain hosting the properly structured active-site Cys residue, as single domain proteins or in combination with distinct protein domains. An increasing number of reports indicate that rhodanese modules are versatile sulfur carriers that have adapted their function to fulfill the need for reactive sulfane sulfur in distinct metabolic and regulatory pathways. Recent investigations have shown that rhodanese domains are also structurally related to the catalytic subunit of Cdc25 phosphatase enzymes and that the two enzyme families are likely to share a common evolutionary origin. In this review, the rhodanese/Cdc25 phosphatase superfamily is analyzed. Although the identification of their biological substrates has thus far proven elusive, the emerging picture points to a role for the amino-acid composition of the active-site loop in substrate recognition/specificity. Furthermore, the frequently observed association of catalytically inactive rhodanese modules with other protein domains suggests a distinct regulatory role for these inactive domains, possibly in connection with signaling.
Bordo
Domenico
D
National Cancer Research Institute, c/o Advanced Biotechnology Center, Genova, Italy. domenico@alcor.ge.infm.it
Bork
Peer
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D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D003545:Cysteine / Q000737:chemistry; D016680:Genome, Bacterial; D008958:Models, Molecular; D005810:Multigene Family; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013884:Thiosulfate Sulfurtransferase / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D013884:Thiosulfate Sulfurtransferase; D020687:cdc25 Phosphatases; D003545:Cysteine