4wya

From Proteopedia

(Difference between revisions)

Revision as of 14:19, 27 April 2017

Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a fragment hit

Structural highlights

4wya is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4wyc, 4wyd, 4wye, 4wyf, 4wyg
Activity:	Adenosylmethionine--8-amino-7-oxononanoate transaminase, with EC number 2.6.1.62
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BIOA_MYCTU] Catalyzes the reversible transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only animotransferase known to utilize SAM as an amino donor. Can also use sinefungin as substrate.^[1]

Publication Abstract from PubMed

The PLP-dependent transaminase (BioA) of Mycobacterium tuberculosis and other pathogens that catalyzes the second step of biotin biosynthesis is a now well-validated target for antibacterial development. Fragment screening by differential scanning fluorimetry has been performed to discover new chemical scaffolds and promote optimization of existing inhibitors. Calorimetry confirms binding of six molecules with high ligand efficiency. Thermodynamic data identifies which molecules bind with the enthalpy driven stabilization preferred in compounds that represent attractive starting points for future optimization. Crystallographic characterization of complexes with these molecules reveals the dynamic nature of the BioA active site. Different side chain conformational states are stabilized in response to binding by different molecules. A detailed analysis of conformational diversity in available BioA structures is presented, resulting in the identification of two states that might be targeted with molecular scaffolds incorporating well-defined conformational attributes. This new structural data can be used as part of a scaffold hopping strategy to further optimize existing inhibitors or create new small molecules with improved therapeutic potential.

Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA.,Dai R, Geders TW, Liu F, Park SW, Schnappinger D, Aldrich CC, Finzel BC J Med Chem. 2015 Jun 24. PMID:26068403^[2]

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

References

↑ Mann S, Ploux O. 7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic target. Characterization and inhibition studies. FEBS J. 2006 Oct;273(20):4778-89. Epub 2006 Sep 19. PMID:16984394 doi:10.1111/j.1742-4658.2006.05479.x
↑ Dai R, Geders TW, Liu F, Park SW, Schnappinger D, Aldrich CC, Finzel BC. Fragment-Based Exploration of Binding Site Flexibility in Mycobacterium tuberculosis BioA. J Med Chem. 2015 Jun 24. PMID:26068403 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00092

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/4wya"

@@ Line 1: / Line 1: @@
 ==Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a fragment hit==
 <StructureSection load='4wya' size='340' side='right' caption='[[4wya]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4wyc|4wyc]], [[4wyd|4wyd]], [[4wye|4wye]], [[4wyf|4wyf]], [[4wyg|4wyg]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylmethionine--8-amino-7-oxononanoate_transaminase Adenosylmethionine--8-amino-7-oxononanoate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.62 2.6.1.62] </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=4wya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wya OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wya RCSB], [http://www.ebi.ac.uk/pdbsum/4wya 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=4wya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wya OCA], [http://pdbe.org/4wya PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wya RCSB], [http://www.ebi.ac.uk/pdbsum/4wya PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wya 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 4wya" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4wya

From Proteopedia

Revision as of 14:19, 27 April 2017

Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a fragment hit

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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