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| [[Image:1z75.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1z75| PDB=1z75 | SCENE= }} | | {{STRUCTURE_1z75| PDB=1z75 | SCENE= }} |
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| '''Crystal Structure of ArnA dehydrogenase (decarboxylase) domain, R619M mutant'''
| | ===Crystal Structure of ArnA dehydrogenase (decarboxylase) domain, R619M 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_15939024}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15939024 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15939024}} |
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| ==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'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 17:09:03 2008'' |