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679 a.a.
Key reference
DOI no: 10.1016/S0969-2126(98)00053-7 Structure 6:521-530 (1998) PubMed id: 9562562
The crystal structure of an intramolecular trans-sialidase with a NeuAc alpha2-->3Gal specificity. Y.Luo, S.C.Li, M.Y.Chou, Y.T.Li, M.Luo. ABSTRACT
BACKGROUND: Intramolecular trans-sialidase from leech (Macrobdella decora) is a unique enzyme which cleaves the terminal neuraminic acid (NeuAc) residue from sialoglycoconjugates, releasing 2, 7-anhydro-neuraminic acid (2,7-anhydro-NeuAc). It is the first enzyme found to exhibit strictly specific cleavage of NeuAc alpha2-->3Gal linkages in sialoglycoconjugates. The release of 2,7-anhydro-NeuAc instead of NeuAc implies a unique mechanism, in which the sialosyl linkage is transferred within the sialoglycoconjugate rather than hydrolyzed. The aims of the structural study were to gain structural insight into the strict specificity and unique mechanism of this unusual enzyme. Results:. The 2.0 A crystal structure of recombinant leech intramolecular trans-sialidase has been solved by multiple isomorphous replacement. The 1.8 A structure of the enzyme in complex with 2-deoxy-2, 3-didehydro-NeuAc was also solved. The refined model comprising residues 81-769 has a catalytic beta-propeller domain (C), a N-terminal lectin-like domain (II) and an irregular beta-stranded domain (III) inserted into the catalytic domain. The structure reveals several possible carbohydrate-binding features: domain II has a concave face, like that of other sialidases, and there is a suitable surface charge distribution at the domain III-C interface. CONCLUSIONS: Structural comparisons showed closer evolutionary relationships to bacterial sialidases than to viral neuraminidases. Mainchain and sidechain atoms around Thr593 make the glycerol-binding pocket incapable of accommodating an extended equatorial 6-glycerol group, implying that the 6-glycerol group of the reaction intermediate may occupy an axial position, which is also required by the catalytic mechanism. The steric hindrance introduced by the bulky sidechain of Trp734 above the 2-carboxylate group may explain the lack of water involvement in the cleavage reaction and the substrate specificity.
Selected figure(s)
Figure 2.
Figure 2. Multidomain architecture of leech IT-sialidase. (a) Ribbon representation of the multidomain structure of leech IT-sialidase. The ordered structure starts with the N-terminal lectin-like domain II in red and continues with the canonical propeller-like catalytic domain C in green. The irregular b-stranded domain III (in blue) is inserted between the two central b strands of the second b sheet of domain C. Neu5Ac2en in the active site is shown as a space-filling model. The suggested carbohydrate-binding residues in the concave face of domain II are shown in ball-and-stick representation. (b,c) Color-coded surface electrostatic potential map (positive in blue, negative in red) of leech IT-sialidase. (b) The face of the active site. (c) The reverse side of the active site.The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 521-530) copyright 1998. Figure was selected by an automated process.
Literature references that cite this PDB file's key reference
PubMed id Reference
19023603 D.C.Soares, P.N.Barlow, D.J.Porteous, and R.S.Devon (2009).
An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin.J Mol Model, 15, 113-122.
19594936 E.M.Quistgaard, and S.S.Thirup (2009).
Sequence and structural analysis of the Asp-box motif and Asp-box beta-propellers; a widespread propeller-type characteristic of the Vps10 domain family and several glycoside hydrolase families.BMC Struct Biol, 9, 46. 18765901 G.Xu, X.Li, P.W.Andrew, and G.L.Taylor (2008).
Structure of the catalytic domain of Streptococcus pneumoniae sialidase NanA.Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 772-775.
PDB codes: 2vvz 2w20
18218621 S.L.Newstead, J.A.Potter, J.C.Wilson, G.Xu, C.H.Chien, A.G.Watts, S.G.Withers, and G.L.Taylor (2008).
The structure of Clostridium perfringens NanI sialidase and its catalytic intermediates.J Biol Chem, 283, 9080-9088.
PDB codes: 2bf6 2vk5 2vk6 2vk7
15608653 K.Stummeyer, A.Dickmanns, M.Mühlenhoff, R.Gerardy-Schahn, and R.Ficner (2005).
Crystal structure of the polysialic acid-degrading endosialidase of bacteriophage K1F.Nat Struct Mol Biol, 12, 90-96.
PDB codes: 1v0e 1v0f
16239725 S.L.Newstead, J.N.Watson, A.J.Bennet, and G.Taylor (2005).
Galactose recognition by the carbohydrate-binding module of a bacterial sialidase.Acta Crystallogr D Biol Crystallogr, 61, 1483-1491.
PDB codes: 2bq9 2bzd
14730352 C.P.Chiu, A.G.Watts, L.L.Lairson, M.Gilbert, D.Lim, W.W.Wakarchuk, S.G.Withers, and N.C.Strynadka (2004).
Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog.Nat Struct Mol Biol, 11, 163-170.
PDB codes: 1ro7 1ro8
15226294 I.Moustafa, H.Connaris, M.Taylor, V.Zaitsev, J.C.Wilson, M.J.Kiefel, M.von Itzstein, and G.Taylor (2004).
Sialic acid recognition by Vibrio cholerae neuraminidase.J Biol Chem, 279, 40819-40826.
PDB codes: 1w0o 1w0p
15502328 S.Newstead, C.H.Chien, M.Taylor, and G.Taylor (2004).
Crystallization and atomic resolution X-ray diffraction of the catalytic domain of the large sialidase, nanI, from Clostridium perfringens.Acta Crystallogr D Biol Crystallogr, 60, 2063-2066.
12071958 G.Montagna, M.L.Cremona, G.Paris, M.F.Amaya, A.Buschiazzo, P.M.Alzari, and A.C.Frasch (2002).
The trans-sialidase from the african trypanosome Trypanosoma brucei.Eur J Biochem, 269, 2941-2950. 10400772 D.Kobasa, S.Kodihalli, M.Luo, M.R.Castrucci, I.Donatelli, Y.Suzuki, T.Suzuki, and Y.Kawaoka (1999).
Amino acid residues contributing to the substrate specificity of the influenza A virus neuraminidase.J Virol, 73, 6743-6751. The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.
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