1b9i

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Revision as of 05:55, 25 December 2014

CRYSTAL STRUCTURE OF 3-AMINO-5-HYDROXYBENZOIC ACID (AHBA) SYNTHASE

Structural highlights

1b9i is a 1 chain structure with sequence from Amycolatopsis mediterranei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[O52552_AMYMD] Catalyzes the dehydration and aromatization of 5-amino-5-deoxy-3-dehydroshikimate (aminoDHS) to 3-amino-5-hydroxybenzoate (AHBA), a compound that then serves as the starter unit for the assembly of a polyketide during the biosynthesis of rifamycin B and other ansamycin antibiotics. Can not utilize 5-deoxy-5-amino-3-dehydroquinate (aminoDHQ), 5-deoxy-5-aminoshikimate (aminoSA), quinate, 3-dehydroquinate, or 3-dehydroshikimate (DHS) as substrate.^[1] ^[2] In a complex with RifL, RifK may have a second function in the AHBA pathway, acting as a transaminase introducing the nitrogen into the first pathway intermediate, UDP-3-keto-D-glucose, to give UDP-kanosamine. Appears to use glutamine as the nitrogen donor; NH(4)+ or asparagine are 30% less effective as nitrogen donors and neither glutamate nor aspartate show activity.^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The biosynthesis of ansamycin antibiotics, including rifamycin B, involves the synthesis of an aromatic precursor, 3-amino-5-hydroxybenzoic acid (AHBA), which serves as starter for the assembly of the antibiotics' polyketide backbone. The terminal enzyme of AHBA formation, AHBA synthase, is a dimeric, pyridoxal 5'-phosphate (PLP) dependent enzyme with pronounced sequence homology to a number of PLP enzymes involved in the biosynthesis of antibiotic sugar moieties. The structure of AHBA synthase from Amycolatopsis mediterranei has been determined to 2.0 A resolution, with bound cofactor, PLP, and in a complex with PLP and an inhibitor (gabaculine). The overall fold of AHBA synthase is similar to that of the aspartate aminotransferase family of PLP-dependent enzymes, with a large domain containing a seven-stranded beta-sheet surrounded by alpha-helices and a smaller domain consisting of a four-stranded antiparallel beta-sheet and four alpha-helices. The uninhibited form of the enzyme shows the cofactor covalently linked to Lys188 in an internal aldimine linkage. On binding the inhibitor, gabaculine, the internal aldimine linkage is broken, and a covalent bond is observed between the cofactor and inhibitor. The active site is composed of residues from two subunits of AHBA synthase, indicating that AHBA synthase is active as a dimer.

Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase.,Eads JC, Beeby M, Scapin G, Yu TW, Floss HG Biochemistry. 1999 Aug 3;38(31):9840-9. PMID:10433690^[5]

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

References

↑ Kim CG, Yu TW, Fryhle CB, Handa S, Floss HG. 3-Amino-5-hydroxybenzoic acid synthase, the terminal enzyme in the formation of the precursor of mC7N units in rifamycin and related antibiotics. J Biol Chem. 1998 Mar 13;273(11):6030-40. PMID:9497318
↑ Floss HG, Yu TW, Arakawa K. The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review. J Antibiot (Tokyo). 2011 Jan;64(1):35-44. doi: 10.1038/ja.2010.139. Epub 2010 Nov, 17. PMID:21081954 doi:http://dx.doi.org/10.1038/ja.2010.139
↑ Kim CG, Yu TW, Fryhle CB, Handa S, Floss HG. 3-Amino-5-hydroxybenzoic acid synthase, the terminal enzyme in the formation of the precursor of mC7N units in rifamycin and related antibiotics. J Biol Chem. 1998 Mar 13;273(11):6030-40. PMID:9497318
↑ Floss HG, Yu TW, Arakawa K. The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review. J Antibiot (Tokyo). 2011 Jan;64(1):35-44. doi: 10.1038/ja.2010.139. Epub 2010 Nov, 17. PMID:21081954 doi:http://dx.doi.org/10.1038/ja.2010.139
↑ Eads JC, Beeby M, Scapin G, Yu TW, Floss HG. Crystal structure of 3-amino-5-hydroxybenzoic acid (AHBA) synthase. Biochemistry. 1999 Aug 3;38(31):9840-9. PMID:10433690 doi:10.1021/bi990018q

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1b9i"

@@ Line 6: / Line 6: @@
 <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=1b9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b9i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1b9i RCSB], [http://www.ebi.ac.uk/pdbsum/1b9i PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/O52552_AMYMD O52552_AMYMD]] Catalyzes the dehydration and aromatization of 5-amino-5-deoxy-3-dehydroshikimate (aminoDHS) to 3-amino-5-hydroxybenzoate (AHBA), a compound that then serves as the starter unit for the assembly of a polyketide during the biosynthesis of rifamycin B and other ansamycin antibiotics. Can not utilize 5-deoxy-5-amino-3-dehydroquinate (aminoDHQ), 5-deoxy-5-aminoshikimate (aminoSA), quinate, 3-dehydroquinate, or 3-dehydroshikimate (DHS) as substrate.<ref>PMID:9497318</ref> <ref>PMID:21081954</ref>   In a complex with RifL, RifK may have a second function in the AHBA pathway, acting as a transaminase introducing the nitrogen into the first pathway intermediate, UDP-3-keto-D-glucose, to give UDP-kanosamine. Appears to use glutamine as the nitrogen donor; NH(4)+ or asparagine are 30% less effective as nitrogen donors and neither glutamate nor aspartate show activity.<ref>PMID:9497318</ref> <ref>PMID:21081954</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1b9i

From Proteopedia

Revision as of 05:55, 25 December 2014

CRYSTAL STRUCTURE OF 3-AMINO-5-HYDROXYBENZOIC ACID (AHBA) SYNTHASE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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