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4oca

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Revision as of 22:13, 4 August 2016

Cryatal structure of ArnB K188A complexted with PLP and UDP-Ara4N

Structural highlights

4oca is a 1 chain structure with sequence from "bacillus_typhimurium"_loeffler_1892 "bacillus typhimurium" loeffler 1892. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	yfbE, arnB ("Bacillus typhimurium" Loeffler 1892)
Activity:	UDP-4-amino-4-deoxy-L-arabinose aminotransferase, with EC number 2.6.1.87
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[F5ZUF5_SALTU] Catalyzes the conversion of UDP-4-keto-arabinose (UDP-Ara4O) to UDP-4-amino-4-deoxy-L-arabinose (UDP-L-Ara4N). The modified arabinose is attached to lipid A and is required for resistance to polymyxin and cationic antimicrobial peptides (By similarity).[HAMAP-Rule:MF_01167][SAAS:SAAS022850_004_033570]

Publication Abstract from PubMed

Cationic Antimicrobial Peptides (CAMPs) represent a first line of defense against bacterial colonization. When fighting Gram-negative bacteria, CAMPs initially interact electrostatically with the negatively charged phosphate groups in lipid A and are thought to kill bacteria by disrupting their membrane integrity. However, many human pathogens, including Salmonella and Pseudomonas , have evolved lipid A modification mechanisms that result in resistance to CAMPs and related antibiotics such as Colistin. The addition of 4-amino-4-deoxy-l-Arabinose (Ara4N) to a phosphate group in lipid A is one such modification, frequently found in Pseudomonas isolated from cystic fibrosis patients. The pathway for biosynthesis of Ara4N-lipid A requires conversion of UDP-Glucuronic acid into UDP-Ara4N and subsequent transfer of the amino-sugar to lipid A. ArnB is a pyridoxal-phosphate (PLP) dependent transaminase that catalyzes a crucial step in the pathway: synthesis of UDP-Ara4N from UDP-4-keto-pentose. Here we present the 2.3 A resolution crystal structure of an active site mutant of ArnB (K188A) in complex with the reaction intermediate aldimine formed by UDP-Ara4N and PLP. The sugar-nucleotide binding site is in a cleft between the subunits of the ArnB dimer with the uracil buried at the interface and the UDP ribose and phosphate groups exposed to the solvent. The Ara4N moiety is found in the (4)C1 conformation and its positioning, stabilized by interactions with both the protein and cofactor, is compatible with catalysis. The structure suggests strategies for the development of specific inhibitors that may prove useful in the treatment of resistant bacteria such as Pseudomonas found in cystic fibrosis patients.

Structural Basis for Substrate Specificity in ArnB. A Key Enzyme in the Polymyxin Resistance Pathway of Gram-Negative Bacteria.,Lee M, Sousa MC Biochemistry. 2014 Feb 4;53(4):796-805. doi: 10.1021/bi4015677. Epub 2014 Jan 24. PMID:24460375^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lee M, Sousa MC. Structural Basis for Substrate Specificity in ArnB. A Key Enzyme in the Polymyxin Resistance Pathway of Gram-Negative Bacteria. Biochemistry. 2014 Feb 4;53(4):796-805. doi: 10.1021/bi4015677. Epub 2014 Jan 24. PMID:24460375 doi:http://dx.doi.org/10.1021/bi4015677

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4oca"

@@ Line 1: / Line 1: @@
 ==Cryatal structure of ArnB K188A complexted with PLP and UDP-Ara4N==
 <StructureSection load='4oca' size='340' side='right' caption='[[4oca]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">yfbE, arnB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=90371 "Bacillus typhimurium" Loeffler 1892])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-4-amino-4-deoxy-L-arabinose_aminotransferase UDP-4-amino-4-deoxy-L-arabinose aminotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.87 2.6.1.87] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4oca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oca OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oca RCSB], [http://www.ebi.ac.uk/pdbsum/4oca PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4oca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oca OCA], [http://pdbe.org/4oca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oca RCSB], [http://www.ebi.ac.uk/pdbsum/4oca PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oca ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4oca" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4oca

From Proteopedia

Revision as of 22:13, 4 August 2016

Cryatal structure of ArnB K188A complexted with PLP and UDP-Ara4N

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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