1f73

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spinqualitylabelsall models 1f73, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE ANALYSIS OF N-ACETYLNEURAMINATE LYASE FROM HAEMOPHILUS INFLUENZAE: CRYSTAL FORM III IN COMPLEX WITH SIALIC ACID ALDITOL

Overview

The N-acetylneuraminate lyase (NAL) sub-family of (beta/alpha)(8) enzymes, share a common catalytic step but catalyse reactions in different, biological pathways. Known examples include NAL, dihydrodipicolinate, synthetase (DHDPS), d-5-keto-4-deoxyglucarate dehydratase, 2-keto-3-deoxygluconate aldolase, trans-o-hydroxybenzylidenepyruvate, hydrolase-aldolase and trans-2'-carboxybenzalpyruvate hydratase-aldolase., Little is known about the way in which the three-dimensional structure of, the respective active sites are modulated across the sub-family to achieve, cognate substrate recognition. We present here the structure of, Haemophilus influenzae NAL determined by X-ray crystallography to a, maximum resolution of 1.60 A, in native form and in complex with three, substrate analogues (sialic acid alditol, 4-deoxy-sialic acid and, 4-oxo-sialic acid). These structures reveal for the first time the mode of, binding of the complete substrate in the NAL active site. On the basis of, the above structures, that of substrate-complexed DHDPS and sequence, comparison across the sub-family we are able to propose a unified model, for active site modulation. The model is one of economy, allowing wherever, appropriate the retention or relocation of residues associated with, binding common substrate substituent groups. Our structures also suggest a, role for the strictly conserved tyrosine residue found in all active sites, of the sub-family, namely that it mediates proton abstraction by the, alpha-keto acid carboxylate in a substrate-assisted catalytic reaction, pathway.

About this Structure

1F73 is a Single protein structure of sequence from Haemolphilus influenzae with HMN and GOL as ligands. Active as N-acetylneuraminate lyase, with EC number 4.1.3.3 Full crystallographic information is available from OCA.

Reference

Active site modulation in the N-acetylneuraminate lyase sub-family as revealed by the structure of the inhibitor-complexed Haemophilus influenzae enzyme., Barbosa JA, Smith BJ, DeGori R, Ooi HC, Marcuccio SM, Campi EM, Jackson WR, Brossmer R, Sommer M, Lawrence MC, J Mol Biol. 2000 Oct 27;303(3):405-21. PMID:11031117

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