Sequence and structural features of the T-fold, an original tunnelling building unit.
A similar fold has been found in four archetype enzymes that perform different functions. This new fold has been named the T-fold because it is found in multimeric proteins crossed by a tunnel. The T-fold consists of an antiparallel beta-sheet of four sequential strands, and two antiparallel helices between the second and third strand, layered on the concave side of the beta-sheet. The presently known T-fold proteins share a high structural similarity (a mean of 1.4 A root mean square (r.m.s.) deviation on the common core) while they only exhibit a low level of sequence identity (a mean of 10.5% on the aligned regions). They bind to substrates belonging to the purine or pterin families, and share a fold-related binding site with a glutamate or glutamine residue anchoring the substrate and a lot of conserved interactions. They also share a similar oligomerization mode: several T-folds join together to form a beta(2n)alpha(n) barrel, then two barrels join together in a head-to-head fashion to made up the native enzymes. The T-fold has the characteristics of a globular domain, with a hydrophobic core and a clearly defined topohydrophobic network. It defines a new class of common folds or recurrent domains found in distantly related proteins. However, it is likely not stable in monomeric form and until now is only observed in association with other T-folds through multimerization. Proteins 2000;39:142-154.
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Laboratoire de Minéralogie-Cristallographie, équipe Systémes Moléculaires et Biologie Structurale, CNRS UMR 7590, Universités Paris VI et Paris VII, Paris, France.
Poupon
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Mornon
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D000446:Aldehyde-Lyases / Q000737:chemistry; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004798:Enzymes / Q000737:chemistry*; D006136:GTP Cyclohydrolase / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011622:Pterins; D011687:Purines; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014503:Urate Oxidase / Q000737:chemistry
D004798:Enzymes; D011622:Pterins; D011687:Purines; D014503:Urate Oxidase; D006136:GTP Cyclohydrolase; D000446:Aldehyde-Lyases; C020044:dihydroneopterin aldolase; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase