2SIL

THE STRUCTURES OF SALMONELLA TYPHIMURIUM LT2 NEURAMINIDASE AND ITS COMPLEX WITH A TRANSITION STATE ANALOGUE AT 1.6 ANGSTROMS RESOLUTION

Replaces:  1SIL

Summary for 2SIL

• Entry DOI: 10.2210/pdb2sil/pdb
• Descriptor: SIALIDASE (2 entities in total)
• Functional Keywords: hydrolase
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 1
• Total formula weight: 41991.79

Authors

Taylor, G.L.,Crennell, S.J.,Garman, E.F.,Vimr, E.R.,Laver, W.G. (deposition date: 1994-07-13, release date: 1994-08-31, Last modification date: 2024-10-23)

Primary citation

Crennell, S.J.,Garman, E.F.,Philippon, C.,Vasella, A.,Laver, W.G.,Vimr, E.R.,Taylor, G.L.
The structures of Salmonella typhimurium LT2 neuraminidase and its complexes with three inhibitors at high resolution.
J.Mol.Biol., 259:264-280, 1996

PubMed 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.

PubMed: 8656428
DOI: 10.1006/jmbi.1996.0318

Experimental method

X-RAY DIFFRACTION (1.6 Å)