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PDBsum entry 2sim

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Hydrolase PDB id
2sim
Jmol
Contents
Protein chain
381 a.a.
Ligands
DAN
Waters ×242

References listed in PDB file
Key reference
Title The structures of salmonella typhimurium lt2 neuraminidase and its complexes with three inhibitors at high resolution.
Authors S.J.Crennell, E.F.Garman, C.Philippon, A.Vasella, W.G.Laver, E.R.Vimr, G.L.Taylor.
Ref. J Mol Biol, 1996, 259, 264-280. [DOI no: 10.1006/jmbi.1996.0318]
PubMed id 8656428
Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 80%.
Abstract
The structure of Salmonella typhimurium LT2 neuraminidase (STNA) is reported here to a resolution of 1.6 angstroms together with the structures of three complexes of STNA with different inhibitors. The first is 2-deoxy-2,3-dehydro-N-acetyl-neuraminic acid (Neu5Ac2en or DANA), the second and third are phosphonate derivatives of N-acetyl-neuraminic acid (NANA) which have phosphonate groups at the C2 position equatorial (ePANA) and axial (aPANA) to the plane of the sugar ring. The complex structures are at resolutions of 1.6 angstroms, 1.6 angstroms and 1.9 angstroms, respectively. These analyses show the STNA active site to be topologically inflexible and the interactions to be dominated by the arginine triad, with the pyranose rings of the inhibitors undergoing distortion to occupy the space available. Solvent structure differs only around the third phosphonate oxygen, which attracts a potassium ion. The STNA structure is topologically identical to the previously reported influenza virus neuraminidase structures, although very different in detail; the root-mean-square (r.m.s) deviation for 210 C alpha positions considered equivalent is 2.28 angstroms (out of a total of 390 residues in influenza and 381 in STNA). The active site residues are more highly conserved, in that both the viral and bacterial structures contain an arginine triad, a hydrophobic pocket, a tyrosine and glutamic acid residue at the base of the site and a potential proton-donating aspartic acid. However, differences in binding to O4 and to the glycerol side-chain may reflect the different kinetics employed by the two enzymes.
Figure 2.
Figure 2. Stereo views of (a) the STNA C a trace (which has every tenth C a atom numbered) and (b) the B/Beijing monomer C a trace in the same orientation. The regions of the molecules which are within 1.5 Å in this superimposition are coloured red, the rest, black. A DANA molecule marks the position of the active site.
Figure 3.
Figure 3. Stereo views of (a) the S. typhimurium neuraminidase and (b) the B/Beijing influenza neuraminidase active sites with the DANA molecule (light bonds) bound and active site water molecules drawn as two concentric circles. Hydrogen bonds are shown as broken lines.
The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 259, 264-280) copyright 1996.
Secondary reference #1
Title Crystal structure of a bacterial sialidase (from salmonella typhimurium lt2) shows the same fold as an influenza virus neuraminidase.
Authors S.J.Crennell, E.F.Garman, W.G.Laver, E.R.Vimr, G.L.Taylor.
Ref. Proc Natl Acad Sci U S A, 1993, 90, 9852-9856. [DOI no: 10.1073/pnas.90.21.9852]
PubMed id 8234325
Full text Abstract
Secondary reference #2
Title Purification, Crystallization and preliminary crystallographic study of neuraminidase from vibrio cholerae and salmonella typhimurium lt2.
Authors G.Taylor, E.Vimr, E.Garman, G.Laver.
Ref. J Mol Biol, 1992, 226, 1287-1290. [DOI no: 10.1016/0022-2836(92)91069-2]
PubMed id 1518058
Full text Abstract
Figure 1.
Figure 1. Electrophoretic profiles of bacterial neuram- inidases used for crystallizations. pproximately pg of purified recombinant V. cholerae (lane B) and S. typhimurium LT2 (lane C) neuraminidases were fractionated by sodium dodecyl sulphate/poyacrylamid gel electrophoresis, 12.5% separating gel, and visualized by staining with Coomassie brilliant blue. lectrophoresis conditions and molecular weight markers, umbered in kDa on the left (lane A), were as described by Hoyer et l. (1991).
The above figure is reproduced from the cited reference with permission from Elsevier
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