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Crystal structures and proposed structural/functional classification of three protozoan proteins from the isochorismatase superfamily
Author(s) -
Caruthers Jonathan,
Zucker Frank,
Worthey Elizabeth,
Myler Peter J.,
Buckner Fred,
Van Voorhuis Wes,
Mehlin Chris,
Boni Erica,
Feist Tiffany,
Luft Joseph,
Gulde Stacey,
Lauricella Angela,
Kaluzhniy Oleksandr,
Anderson Lori,
Le Trong Isolde,
Holmes Margaret A.,
Earnest Thomas,
Soltis Michael,
Hodgson Keith O.,
Hol Wim G.J.,
Merritt Ethan A.
Publication year - 2005
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.051783005
Subject(s) - subfamily , protein superfamily , biology , hydrolase , biochemistry , active site , cysteine , periplasmic space , protein structure , protein subunit , sequence alignment , structural motif , tetramer , protein family , peptide sequence , enzyme , gene , escherichia coli
We have determined the crystal structures of three homologous proteins from the pathogenic protozoans Leishmania donovani, Leishmania major , and Trypanosoma cruzi . We propose that these proteins represent a new subfamily within the isochorismatase superfamily (CDD classification cd004310). Their overall fold and key active site residues are structurally homologous both to the biochemically well‐characterized N ‐carbamoylsarcosine‐amidohydrolase, a cysteine hydrolase, and to the phenazine biosynthesis protein PHZD (isochorismase), an aspartyl hydrolase. All three proteins are annotated as mitochondrial‐associated ribonuclease Mar1, based on a previous characterization of the homologous protein from L. tarentolae . This would constitute a new enzymatic activity for this structural superfamily, but this is not strongly supported by the observed structures. In these protozoan proteins, the extended active site is formed by inter‐subunit association within a tetramer, which implies a distinct evolutionary history and substrate specificity from the previously characterized members of the isochorismatase superfamily. The characterization of the active site is supported crystallographically by the presence of an unidentified ligand bound at the active site cysteine of the T. cruzi structure.