1z75: Difference between revisions

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[[Image:1z75.gif|left|200px]]
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[[Image:1z75.png|left|200px]]


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{{STRUCTURE_1z75|  PDB=1z75  |  SCENE=  }}  
{{STRUCTURE_1z75|  PDB=1z75  |  SCENE=  }}  


'''Crystal Structure of ArnA dehydrogenase (decarboxylase) domain, R619M mutant'''
===Crystal Structure of ArnA dehydrogenase (decarboxylase) domain, R619M mutant===




==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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{{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]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 17:15:46 2008''
 
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Revision as of 17:09, 27 July 2008

File:1z75.png

Template:STRUCTURE 1z75

Crystal Structure of ArnA dehydrogenase (decarboxylase) domain, R619M mutantCrystal Structure of ArnA dehydrogenase (decarboxylase) domain, R619M mutant

Template:ABSTRACT PUBMED 15939024

About this StructureAbout this Structure

1Z75 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

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