1z73: Difference between revisions

Revision as of 17:15, 3 May 2008

Crystal Structure of E. coli ArnA dehydrogenase (decarboxylase) domain, S433A mutant

OverviewOverview

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 StructureAbout this Structure

1Z73 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

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

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OCA

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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1z73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z73 OCA], [http://www.ebi.ac.uk/pdbsum/1z73 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1z73 RCSB]</span>
-}}
 '''Crystal Structure of E. coli ArnA dehydrogenase (decarboxylase) domain, S433A mutant'''
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 [[Category: May, A P.]]
 [[Category: Sousa, M C.]]
-[[Category: rossmann fold]]
+[[Category: Rossmann fold]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 17:15:35 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:30:40 2008''