Crystal Structure of Papaya Glutaminyl Cyclase, an Archetype for Plant and Bacterial Glutaminyl Cyclases

Wintjens, René; Belrhali, Hassan; Clantin, Bernard; Azarkan, Mohamed; Bompard, Coralie; Baeyens‐Volant, Danielle; Looze, Yvan; Villeret, Vincent

doi:10.1016/j.jmb.2005.12.029

Cited by 33 publications

(39 citation statements)

References 67 publications

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“…This is a reaction similar to that carried out by GGCT, but the structure of GGCT is clearly unrelated to that of the of the glutaminyl cyclases (31,32). The glutaminyl cyclases are structurally related to the zinc-dependent exopeptidases that catalyze a reaction that is also reminiscent of the cleavage of the ␥-glu- tamyl-amino acid peptide bond catalyzed by GGCT (31).…”

Section: Discussionmentioning

confidence: 99%

“…papaya glutaminyl cyclase (32) and human glutaminyl cyclase (31). The fold is classified as the "BtrG-like" family in SCOP (33), a small family that includes hypothetical proteins from Mus musculus (Protein Data Bank code 1VKB), E. coli (Protein Data Bank code 1XHS), Pyrococcus horikoshii (Protein Data Bank code 1V30), and Arabidopsis thaliana (Protein Data Bank code 2G0Q).…”

Section: Discussionmentioning

confidence: 99%

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The Identification and Structural Characterization of C7orf24 as γ-Glutamyl Cyclotransferase

Oakley

Yamada

Liú

et al. 2008

Journal of Biological Chemistry

112

113

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The hypothetical protein C7orf24 has been implicated as a cancer marker with a potential role in cell proliferation. We have identified C7orf24 as ␥-glutamyl cyclotransferase (GGCT) that catalyzes the formation of 5-oxoproline (pyroglutamic acid) from ␥-glutamyl dipeptides and potentially plays a significant role in glutathione homeostasis. In the present study we have identified the first cDNA clones encoding a ␥-glutamyl cyclotransferase. The GGCT gene is located on chromosome 7p14-15 and consists of four exons that span 8 kb. The primary sequence is 188 amino acids in length and is unlike any protein of known function. We crystallized functional recombinant ␥-glutamyl cyclotransferase and determined its structure at 1.7 Å resolution. The enzyme is a dimer of 20,994-Da subunits. The topology of GGCT is unrelated to other enzymes associated with cyclotransferase-like activity. The fold was originally classified as "BtrG-like," a small family that only includes structures of hypothetical proteins from Mus musculus, Escherichia coli, Pyrococcus horikoshii, and Arabidopsis thaliana. Since this is the first member of this family with a defined function, we propose to refer to this structure as the ␥-glutamyl cyclotransferase fold. We have identified a potential active site pocket that contains a highly conserved glutamic acid (Glu 98 ) and propose that it acts as a general acid/base in the reaction mechanism. Mutation of Glu 98 to Ala or Gln completely inactivates the enzyme without altering the overall fold.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Identification and Structural Characterization of C7orf24 as γ-Glutamyl Cyclotransferase

Oakley

Yamada

Liú

et al. 2008

Journal of Biological Chemistry

112

113

View full text Add to dashboard Cite

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“…Indeed, the active site is located in the equivalent region on the anterior surface of eight β-propeller GH families, polysaccharide lyase family PL22, and even non-CAZyme β-propeller enzymes (Fig. 4) (18). Structural comparison of BT3686 with other β-propeller GHs reveals that highest amino acid conservation, including several invariant residues, is on this anterior side of the enzyme.…”

Section: (17)mentioning

confidence: 99%

Unusual active site location and catalytic apparatus in a glycoside hydrolase family

Muñoz‐Muñoz

Cartmell

Terrapon

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The human gut microbiota use complex carbohydrates as major nutrients. The requirement for an efficient glycan degrading systems exerts a major selection pressure on this microbial community. Thus, we propose that these bacteria represent a substantial resource for discovering novel carbohydrate active enzymes. To test this hypothesis, we focused on enzymes that hydrolyze rhamnosidic bonds, as cleavage of these linkages is chemically challenging and there is a paucity of information on L-rhamnosidases. Here we screened the activity of enzymes derived from the human gut microbiota bacterium Bacteroides thetaiotaomicron, which are up-regulated in response to rhamnose-containing glycans. We identified an α-L-rhamnosidase, BT3686, which is the founding member of a glycoside hydrolase (GH) family, GH145. In contrast to other rhamnosidases, BT3686 cleaved L-Rha-α1,4-D-GlcA linkages through a retaining double-displacement mechanism. The crystal structure of BT3686 showed that the enzyme displayed a type A sevenbladed β-propeller fold. Mutagenesis and crystallographic studies, including the structure of BT3686 in complex with the reaction product GlcA, revealed a location for the active site among β-propeller enzymes cited on the posterior surface of the rhamnosidase. In contrast to the vast majority of GH, the catalytic apparatus of BT3686 does not comprise a pair of carboxylic acid residues but, uniquely, a single histidine functions as the only discernable catalytic amino acid. Intriguingly, the histidine, His48, is not invariant in GH145; however, when engineered into structural homologs lacking the imidazole residue, α-L-rhamnosidase activity was established. The potential contribution of His48 to the catalytic activity of BT3686 is discussed.rhamnosidase | human gut microbiota | gum arabic | Bacteroides thetaiotaomicron | catalytic histidine

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“…Two types of QCs have been defined thus far. Type I QCs were found in plants and in several pathogenic bacteria and human parasites, 1 while type II QCs were mainly identified in the neuroendocrine tissues of mammals. [2][3][4][5][6][7] Up to now, human QC (hQC) is the most extensively studied type II QC, which is known to be important in the maturation of numerous neuropeptides and cytokines in their secretory pathways.…”

Section: Introductionmentioning

confidence: 99%

Crystal Structure and Functional Analysis of the Glutaminyl Cyclase from Xanthomonas campestris

Huang

Wang

et al. 2010

Journal of Molecular Biology

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Crystal Structure of Papaya Glutaminyl Cyclase, an Archetype for Plant and Bacterial Glutaminyl Cyclases

Cited by 33 publications

References 67 publications

The Identification and Structural Characterization of C7orf24 as γ-Glutamyl Cyclotransferase

The Identification and Structural Characterization of C7orf24 as γ-Glutamyl Cyclotransferase

Unusual active site location and catalytic apparatus in a glycoside hydrolase family

Crystal Structure and Functional Analysis of the Glutaminyl Cyclase from Xanthomonas campestris

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