Pantothenate synthetase

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{{STRUCTURE_2a7x| PDB=2a7x | SIZE=400| SCENE= |right|CAPTION=Pantothenate synthetase complex with AMP (stick model), sulfate and glycerol [[2a7x]] }}
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<StructureSection load='' size='450' side='right' caption='Pantothenate synthetase complex with pantoate, AMPPNP, sulfate, Mg+2 ion (green), ethanol and glycerol (PDB entry [[1n2e]])' scene='52/525165/Cv/1' pspeed='8'>
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== Function ==
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'''Pantothenate synthetase''' (PS) catalyzes the ATP-dependent condensation of pantoate and β-alanine to form pantothenate. Pantothenate (vitamin B5) biosynthesis is essential for the virulence of Mycobacterium tuberculosis thus its blockage can be used as a potential drug target.
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'''Pantothenate synthetase''' or '''pantoate-beta-alanine ligase''' (PS) catalyzes the ATP-dependent condensation of pantoate and β-alanine to form pantothenate<ref>PMID:17932772</ref>.
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== Relevance ==
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Pantothenate (vitamin B5) biosynthesis is essential for the virulence of ''Mycobacterium tuberculosis'' thus its blockage can be used as a potential drug target<ref>PMID:26486566</ref>.
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== Structural highlights ==
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PS <scene name='52/525165/Cv/7'>active site is located at the C-terminal of the central parallel β sheet</scene>. In this structure the pantoate substrate electron density is well defined in one subunit while the nucleotide electron density is well defined in the other<ref>PMID:12717031</ref>. Water molecules are shown as red spheres.
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*<scene name='52/525165/Cv/8'>Pantoate binding site</scene> (chain A).
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*<scene name='52/525165/Cv/9'>AMPPNP binding site</scene> (chain B).
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</StructureSection>
==3D structures of pantothenate synthetase==
==3D structures of pantothenate synthetase==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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{{#tree:id=OrganizedByTopic|openlevels=0|
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===PS===
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*'''Pantothenate synthetase'''
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[[1iho]] – EcPS – ''Escherichia coli''<br />
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[[1mop]], [[2a88]], [[3cov]] – MtPS (mutant) – ''Mycobacterium tuberculosis''<br />
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[[1ufv]] - TtPS (mutant) – ''Thermus thermophilus''<br />
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[[1v8f]] - TtPS <br />
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[[2ejc]] - PS – ''Thermotoga maritima''<br />
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[[3mue]] - PS – ''Salmonella typhimurium''<br />
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[[3mxt]] - CjPS – ''Campylobacter jejuni''<br />
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[[3ag5]] - SaPS – ''Staphylococcus aureus''
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===PS binary complex with adenosine derivatives===
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[[1n2g]] - MtPS + AMPCPP <br />
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**[[1iho]] – EcPS – ''Escherichia coli''<br />
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[[2a7x]] - MtPS (mutant) + AMP<br />
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**[[1mop]], [[2a88]], [[3cov]] – MtPS (mutant) – ''Mycobacterium tuberculosis''<br />
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[[3n8h]] - FtPS + AMP – ''Francisella tularensis''<br />
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**[[1ufv]] - TtPS (mutant) – ''Thermus thermophilus''<br />
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[[3q10]] - YpPS + AMP – ''Yersinia pestis''<br />
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**[[1v8f]] - TtPS <br />
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[[3uk2]] - PS + AMP – ''Burkholderia thailandesis''<br />
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**[[2ejc]] - PS – ''Thermotoga maritima''<br />
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[[2a84]] - MtPS (mutant) + ATP<br />
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**[[3mue]] - PS – ''Salmonella typhimurium''<br />
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[[2x3f]] - SaPS + ATP derivative<br />
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**[[3mxt]] - CjPS – ''Campylobacter jejuni''<br />
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[[3inn]] - PS + ATP – ''Brucella melitensis''<br />
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**[[3ag5]] - SaPS – ''Staphylococcus aureus''<br />
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[[3iob]], [[3ioc]], [[3iod]], [[3ioe]] - MtPS (mutant) + adenosine derivative
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**[[5hg0]] - FtPS + SAM – ''Francisella tularensis''<br />
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**[[7tot]] - PS – ''Bartonella henselae''<br />
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===PS binary complex with pantoate derivatives===
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*Pantothenate synthetase binary complex with adenosine derivatives
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[[1n2i]] - MtPS (mutant) + pantoyl adenylate<br />
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**[[1n2g]] - MtPS + AMPCPP <br />
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[[1n2j]] - MtPS (mutant) + pantoate<br />
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**[[2a7x]] - MtPS (mutant) + AMP<br />
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[[1n2o]] - MtPS (mutant) + β-alanine<br />
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**[[3n8h]] - FtPS + AMP <br />
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[[3q12]] - YpPS + pantoate <br />
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**[[3q10]] - YpPS + AMP – ''Yersinia pestis''<br />
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[[3ag6]] - SaPS + pantoyl adenylate<br />
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**[[3uk2]] - PS + AMP – ''Burkholderia thailandesis''<br />
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[[3guz]] - EcPS (mutant) + pantoate
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**[[2a84]] - MtPS (mutant) + ATP<br />
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**[[2x3f]] - SaPS + ATP derivative<br />
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**[[3inn]] - PS + ATP – ''Brucella melitensis''<br />
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**[[3iob]], [[3ioc]], [[3iod]], [[3ioe]] - MtPS (mutant) + adenosine derivative<br />
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**[[5kwv]] – NgPS (mutant) + AMPPNP – ''Neisseria gonorrhoeae''<br />
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*Pantothenate synthetase binary complex with pantoate derivatives
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===PS binary complex with inhibitor===
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**[[1n2i]], [[1n2h]] - MtPS (mutant) + pantoyl adenylate<br />
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**[[1n2j]] - MtPS (mutant) + pantoate<br />
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**[[1n2o]] - MtPS (mutant) + β-alanine<br />
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**[[3q12]] - YpPS + pantoate <br />
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**[[3ag6]] - SaPS + pantoyl adenylate<br />
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**[[3guz]] - EcPS (mutant) + pantoate
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[[3cow]], [[3coy]], [[3coz]], [[3imc]], [[3ime]], [[3img]], [[3iub]], [[3iue]], [[3ivc]], [[3ivg]], [[3ivx]], [[3isj]], [[3le8]], [[4ddh]], [[4ddk]], [[4ddm]], [[4de5]], [[4ef6]], [[4efk]], [[4fzj]], [[4g5f]] - MtPS (mutant) + inhibitor
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*Pantothenate synthetase binary complex with inhibitor
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===PS ternary complex===
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**[[3cow]], [[3coy]], [[3coz]], [[3imc]], [[3ime]], [[3img]], [[3iub]], [[3iue]], [[3ivc]], [[3ivg]], [[3ivx]], [[3isj]], [[3le8]], [[4ddh]], [[4ddk]], [[4ddm]], [[4de5]], [[4ef6]], [[4efk]], [[4fzj]], [[4g5f]], [[4mq6]], [[4mue]], [[4muf]], [[4mug]], [[4muh]], [[4mui]], [[4muj]], [[4muk]], [[4mul]], [[4mun]] - MtPS (mutant) + inhibitor
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[[2a86]] - MtPS (mutant) + β-alanine + AMP<br />
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*Pantothenate synthetase ternary complex
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[[4g5y]] - MtPS (mutant) + thiophene derivative + ATP<br />
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[[3uy4]] - CjPS + pantothenate + AMP<br />
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[[3qtt]] - FtPS + β-alanine + ATP derivative<br />
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[[1n2b]], [[1n2e]] – MtPS + pantoate + AMPCPP
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**[[2a86]] - MtPS (mutant) + β-alanine + AMP<br />
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**[[5ucr]] – NgPS (mutant) + AMP + alanine<br />
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**[[4g5y]] - MtPS (mutant) + thiophene derivative + ATP<br />
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**[[3uy4]] - CjPS + pantothenate + AMP<br />
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**[[3qtt]] - FtPS + β-alanine + ATP derivative<br />
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**[[1n2b]], [[1n2e]] – MtPS + pantoate + AMPCPP
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}}
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Pantothenate synthetase complex with pantoate, AMPPNP, sulfate, Mg+2 ion (green), ethanol and glycerol (PDB entry 1n2e)

Drag the structure with the mouse to rotate

3D structures of pantothenate synthetase

Updated on 21-August-2023

References

  1. ↑ Jonczyk R, Ronconi S, Rychlik M, Genschel U. Pantothenate synthetase is essential but not limiting for pantothenate biosynthesis in Arabidopsis. Plant Mol Biol. 2008 Jan;66(1-2):1-14. Epub 2007 Oct 12. PMID:17932772 doi:http://dx.doi.org/10.1007/s11103-007-9248-6
  2. ↑ Hung AW, Silvestre HL, Wen S, George GP, Boland J, Blundell TL, Ciulli A, Abell C. Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis. ChemMedChem. 2016 Jan 5;11(1):38-42. doi: 10.1002/cmdc.201500414. Epub 2015 Oct, 21. PMID:26486566 doi:http://dx.doi.org/10.1002/cmdc.201500414
  3. ↑ Wang S, Eisenberg D. Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate. Protein Sci. 2003 May;12(5):1097-108. PMID:12717031

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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