1z74

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{{STRUCTURE_1z74| PDB=1z74 | SCENE= }}
{{STRUCTURE_1z74| PDB=1z74 | SCENE= }}
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'''Crystal Structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619Y mutant'''
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===Crystal Structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619Y mutant===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15939024 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15939024}}
==About this Structure==
==About this Structure==
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[[Category: Sousa, M C.]]
[[Category: Sousa, M C.]]
[[Category: Rossmann fold]]
[[Category: Rossmann fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:15:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:14:59 2008''

Revision as of 00:15, 29 July 2008

Image:1z74.png

Template:STRUCTURE 1z74

Crystal Structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619Y mutant

Template:ABSTRACT PUBMED 15939024

About this Structure

1Z74 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

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