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1xuz

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{{STRUCTURE_1xuz| PDB=1xuz | SCENE= }}
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'''Crystal structure analysis of sialic acid synthase (NeuB)from Neisseria meningitidis, bound to Mn2+, Phosphoenolpyruvate, and N-acetyl mannosaminitol'''
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===Crystal structure analysis of sialic acid synthase (NeuB)from Neisseria meningitidis, bound to Mn2+, Phosphoenolpyruvate, and N-acetyl mannosaminitol===
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==Overview==
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In Neisseria meningitidis and related bacterial pathogens, sialic acids play critical roles in mammalian cell immunity evasion and are synthesized by a conserved enzymatic pathway that includes sialic acid synthase (NeuB, SiaC, or SynC). NeuB catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine, directly forming N-acetylneuraminic acid (or sialic acid). In this paper we report the development of a coupled assay to monitor NeuB reaction kinetics and an 18O-labeling study that demonstrates the synthase operates via a C-O bond cleavage mechanism. We also report the first structure of a sialic acid synthase, that of NeuB, revealing a unique domain-swapped homodimer architecture consisting of a (beta/alpha)8 barrel (TIM barrel)-type fold at the N-terminal end and a domain with high sequence identity and structural similarity to the ice binding type III antifreeze proteins at the C-terminal end of the enzyme. We have determined the structures of NeuB in the malate-bound form and with bound PEP and the substrate analog N-acetylmannosaminitol to 1.9 and 2.2 A resolution, respectively. Typical of other TIM barrel proteins, the active site of NeuB is located in a cavity at the C-terminal end of the barrel; however, the positioning of the swapped antifreeze-like domain from the adjacent monomer provides key residues for hydrogen bonding with substrates in the active site of NeuB, a structural feature that leads to distinct modes of substrate binding from other PEP-utilizing enzymes that lack an analogous antifreeze-like domain. Our observation of a direct interaction between a highly ordered manganese and the N-acetylmannosaminitol in the NeuB active site also suggests an essential role for the ion as an electrophilic catalyst that activates the N-acetylmannosamine carbonyl to the addition of PEP.
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==About this Structure==
==About this Structure==
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[[Category: Domain-swapped dimer]]
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[[Category: Tim barrel]]
[[Category: Tim barrel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 13:44:28 2008''

Revision as of 10:44, 29 July 2008

Image:1xuz.png

Template:STRUCTURE 1xuz

Crystal structure analysis of sialic acid synthase (NeuB)from Neisseria meningitidis, bound to Mn2+, Phosphoenolpyruvate, and N-acetyl mannosaminitol

Template:ABSTRACT PUBMED 15516336

About this Structure

1XUZ is a Single protein structure of sequence from Neisseria meningitidis. Full crystallographic information is available from OCA.

Reference

Structural and mechanistic analysis of sialic acid synthase NeuB from Neisseria meningitidis in complex with Mn2+, phosphoenolpyruvate, and N-acetylmannosaminitol., Gunawan J, Simard D, Gilbert M, Lovering AL, Wakarchuk WW, Tanner ME, Strynadka NC, J Biol Chem. 2005 Feb 4;280(5):3555-63. Epub 2004 Oct 29. PMID:15516336

Page seeded by OCA on Tue Jul 29 13:44:28 2008

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