Crystal structure of a conserved hypothetical protein (gi: 13879369) from <i>Mouse</i> at 1.90 Å resolution reveals a new fold

Klock, Heath E.; Schwarzenbacher, Robert; Xu, Qingping; McMullan, Daniel; Abdubek, Polat; Ambing, Eileen; Axelrod, Herbert L.; Biorac, Tanya; Cánaves, Jaume M.; Chiu, Hsiu‐Ju; Deacon, Ashley M.; DiDonato, Michael; Elsliger, Marc‐André; Godzik, Adam; Grittini, Carina; Grzechnik, Slawomir K.; Hale, Joanna; Hampton, Eric; Han, Gye Won; Haugen, Justin; Hornsby, Michael; Jaroszewski, Lukasz; Koesema, Eric; Kreusch, Andreas; Kühn, Peter; Miller, Mitchell D.; Moy, Kin; Nigoghossian, Edward; Paulsen, Jessica; Quijano, Kevin; Reyes, Ron; Rife, Chris; Sims, Eric; Spraggon, Glen; Stevens, Raymond C.; Bedem, Henry van den; Velasquez, Jeff; Vincent, Juli; White, Aprilfawn; Wolf, Guenter; Wooley, John; Lesley, Scott A.; Wilson, Ian A.

doi:10.1002/prot.20610

Cited by 9 publications

(12 citation statements)

References 18 publications

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“…value of 2.31 Å over 105 aligned C atoms and a sequence identity of 21%, hypothetical protein PH0828 from Pyrococcus horikoshii (PDB code 1v30; Tajika et al, 2004) has an r.m.s.d. value of 2.58 Å over 115 aligned C atoms and a sequence identity of 17% and mouse protein 13879369 (PDB code 1vkb; Klock et al, 2005) has an r.m.s.d. value of 2.81 Å over 118 aligned C atoms and a sequence identity of 15%.…”

Section: Resultsmentioning

confidence: 99%

“…2(b). It was proposed that this cavity serves as an active site for the protein (Klock et al, 2005;Tajika et al, 2004). Further comparison of the UPF0131 family sequences to At5g39720.1 and other AIG2-like proteins revealed the substitution of a strictly conserved solvent-accessible glutamate residue by lysine (Lys74) in all of the AIG2-like plant sequences, indicating a possible functional role for this residue.…”

Section: Resultsmentioning

confidence: 99%

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Solution structure ofArabidopsis thalianaprotein At5g39720.1, a member of the AIG2-like protein family

et al. 2006

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The three-dimensional structure of Arabidopsis thaliana protein At5g39720.1 was determined by NMR spectroscopy. It is the first representative structure of Pfam family PF06094, which contains protein sequences similar to that of AIG2, an A. thaliana protein of unknown function induced upon infection by the bacterial pathogen Pseudomonas syringae. The At5g39720.1 structure consists of a five-stranded -barrel surrounded by two -helices and a small -sheet. A long flexible -helix protrudes from the structure at the C-terminal end. A structural homology search revealed similarity to three members of Pfam family UPF0131. Conservation of residues in a hydrophilic cavity able to bind small ligands in UPF0131 proteins suggests that this may also serve as an active site in AIG2-like proteins.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Solution structure ofArabidopsis thalianaprotein At5g39720.1, a member of the AIG2-like protein family

et al. 2006

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“…1B and 3A) unambiguously identifies the active site. The GGACT residues in proximity to this entity, Tyr 7 98 , and Tyr 105 in GGCT, respectively, strongly suggesting that this compound binds in an analogous fashion in both enzymes. A model of the 5-oxo-L-proline-GGCT complex was therefore produced (Fig.…”

Section: Discussionmentioning

confidence: 96%

“…The loop containing residues 7-10 has a backbone conformation that causes the main chain amino groups to be oriented into the cavity. The oxoproline carboxylic acid moiety accepts hydrogen bonds from the main chain amino groups of Tyr 7 and Gly 8 . The carbonyl oxygen of oxoproline accepts a hydrogen bond from the backbone amino and side chain O-␥ moieties of Thr 9 .…”

mentioning

confidence: 99%

Identification and Characterization of γ-Glutamylamine Cyclotransferase, an Enzyme Responsible for γ-Glutamyl-ϵ-lysine Catabolism

Oakley

Coggan

Board

2010

Journal of Biological Chemistry

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␥-Glutamylamine cyclotransferase (GGACT) is an enzyme that converts ␥-glutamylamines to free amines and 5-oxoproline. GGACT shows high activity toward ␥-glutamyl-⑀-lysine, derived from the breakdown of fibrin and other proteins crosslinked by transglutaminases. The enzyme adopts the newly identified cyclotransferase fold, observed in ␥-glutamylcyclotransferase (GGCT), an enzyme with activity toward ␥-glutamyl-␣-amino acids (Oakley, A. J., Yamada, T., Liu, D., Coggan, M., Clark, A. G., and Board, P. G. (2008) J. Biol. Chem. 283, 22031-22042). Despite the absence of significant sequence identity, several residues are conserved in the active sites of GGCT and GGACT, including a putative catalytic acid/base residue (GGACT Glu 82 ). The structure of GGACT in complex with the reaction product 5-oxoproline provides evidence for a common catalytic mechanism in both enzymes. The proposed mechanism, combined with the three-dimensional structures, also explains the different substrate specificities of these enzymes. Despite significant sequence divergence, there are at least three subfamilies in prokaryotes and eukaryotes that have conserved the GGCT fold and GGCT enzymatic activity.Proteins can be cross-linked via the side chains of glutamine and lysine by transglutaminases. This reaction results in the formation of ammonia and an L-␥-glutamyl-L-⑀-lysine isopeptide bond linking the two polypeptide chains. The existence of such ␥-glutamyl-⑀-lysine links was unambiguously demonstrated in factor XIIIa-cross-linked fibrin: extensive proteolytic degradation of cross-linked fibrin resulted in the formation of L-␥-glutamyl-L-⑀-lysine (1). It was concluded that L-␥-glutamyl-L-⑀-lysine is not broken down by conventional proteolysis. The breakdown of the isodipeptide is instead catalyzed by ␥-glutamylamine cyclotransferase (GGACT), 2 first purified from rabbit kidney (2, 3). The partially purified enzyme was demonstrated to be active toward a range of L-␥-glutamyl conjugates with mono-and polyamines and amino acids. The action of GGACT in all cases is to cyclize the ␥-glutamyl moiety, producing 5-oxo-L-proline and the free alkylamine. No activity was detected toward L-glutamine or L-␤-aspartyl-L-⑀-lysine. Furthermore, derivatives of L-␥-glutamyl-L-⑀-lysine in which the ␣-amino or ␣-carboxyl functional group of the glutamyl moiety is blocked do not serve as substrates, nor do any of a range of L-␥-glutamyl-L-␣-amino acids (3). Based on these results, it was proposed that GGACT functions in the latter stages of the catabolism of the products of transglutaminases (3).We reported recently the identification, cloning, and threedimensional structure of an enzyme with related catalytic activity to GGACT but with distinct specificity: ␥-glutamylcyclotransferase (GGCT) (4). Unlike GGACT, this enzyme is active toward a range of L-␥-glutamyl-␣-amino acids (5, 6). GGCT catalyzes the penultimate step in glutathione catabolism, whereby L-␥-glutamyl-L-␣-cysteine and other L-␥-glutamyl-L-␣-amino acid dipeptides formed by the ␥-glutamyl cycle are c...

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“…Their analysis of two globular proteins, a Thermotoga maritima anti- σ factor antagonist, and a mouse γ -Glutamylamine Cyclotransferase 46 , obtained with NMR and cryogenic X-ray crystallography, determined that sites that exhibit conformational exchange on the millisecond timescale and show elevated conformational variability in NMR solution only, coincided with active sites. In the crystal structures, polar residues generally adopted conformations to satisfy hydrogen-bonding interactions among each other or with the components of the buffer.…”

Section: Solution Nmr Signals Are Generated By Multiple Conformationsmentioning

confidence: 99%

Integrative, dynamic structural biology at atomic resolution—it's about time

Bedem¹,

Fraser²

2015

Nat Methods

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236

171

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Biomolecules adopt a dynamic ensemble of conformations, each with the potential to interact with binding partners or perform the chemical reactions required for a multitude of cellular functions. Recent advances in X-ray crystallography, Nuclear Magnetic Resonance (NMR) spectroscopy, and other techniques are helping us realize the dream of seeing—in atomic detail—how different parts of biomolecules exchange between functional sub-states using concerted motions. Integrative structural biology has advanced our understanding of the formation of large macromolecular complexes and how their components interact in assemblies by leveraging data from many low-resolution methods. Here, we review the growing opportunities for integrative, dynamic structural biology at the atomic scale, contending there is increasing synergistic potential between X-ray crystallography, NMR, and computer simulations to reveal a structural basis for protein conformational dynamics at high resolution.

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Crystal structure of a conserved hypothetical protein (gi: 13879369) from Mouse at 1.90 Å resolution reveals a new fold

Cited by 9 publications

References 18 publications

Solution structure ofArabidopsis thalianaprotein At5g39720.1, a member of the AIG2-like protein family

Solution structure ofArabidopsis thalianaprotein At5g39720.1, a member of the AIG2-like protein family

Identification and Characterization of γ-Glutamylamine Cyclotransferase, an Enzyme Responsible for γ-Glutamyl-ϵ-lysine Catabolism

Integrative, dynamic structural biology at atomic resolution—it's about time

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