1z73
From Proteopedia
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'''Crystal Structure of E. coli ArnA dehydrogenase (decarboxylase) domain, S433A mutant''' | '''Crystal Structure of E. coli ArnA dehydrogenase (decarboxylase) domain, S433A mutant''' | ||
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[[Category: May, A P.]] | [[Category: May, A P.]] | ||
[[Category: Sousa, M C.]] | [[Category: Sousa, M C.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:15:35 2008'' | |
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Revision as of 14:15, 3 May 2008
Crystal Structure of E. coli ArnA dehydrogenase (decarboxylase) domain, S433A mutant
Overview
The modification of lipid A with 4-amino-4-deoxy-L-arabinose (Ara4N) allows gram-negative bacteria to resist the antimicrobial activity of cationic antimicrobial peptides and antibiotics such as polymyxin. ArnA is the first enzyme specific to the lipid A-Ara4N pathway. It contains two functionally and physically separable domains: a dehydrogenase domain (ArnA_DH) catalyzing the NAD+-dependent oxidative decarboxylation of UDP-Glucuronic acid (UDP-GlcA), and a transformylase domain that formylates UDP-Ara4N. Here, we describe the crystal structure of the full-length bifunctional ArnA with UDP-GlcA and ATP bound to the dehydrogenase domain. Binding of UDP-GlcA triggers a 17 A conformational change in ArnA_DH that opens the NAD+ binding site while trapping UDP-GlcA. We propose an ordered mechanism of substrate binding and product release. Mutation of residues R619 and S433 demonstrates their importance in catalysis and suggests that R619 functions as a general acid in catalysis. The proposed mechanism for ArnA_DH has important implications for the design of selective inhibitors.
About this Structure
1Z73 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Structure and mechanism of ArnA: conformational change implies ordered dehydrogenase mechanism in key enzyme for polymyxin resistance., Gatzeva-Topalova PZ, May AP, Sousa MC, Structure. 2005 Jun;13(6):929-42. PMID:15939024 Page seeded by OCA on Sat May 3 17:15:35 2008
