Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 553 - 563 |
| Number of pages | 11 |
| Journal | Acta Crystallographica Section D: Biological Crystallography |
| Volume | 68 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2012 |
Cite this
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Structure of phosphoserine aminotransferase from Mycobacterium tuberculosis. / Coulibaly, Fasseli J; Lassalle, Edouard; Baker, Heather M; Baker, Edward N.
In: Acta Crystallographica Section D: Biological Crystallography, Vol. 68, No. 5, 2012, p. 553 - 563.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Structure of phosphoserine aminotransferase from Mycobacterium tuberculosis
AU - Coulibaly, Fasseli J
AU - Lassalle, Edouard
AU - Baker, Heather M
AU - Baker, Edward N
PY - 2012
Y1 - 2012
N2 - Mycobacterium tuberculosis (Mtb), the causative agent of TB, remains a serious world health problem owing to limitations of the available drugs and the emergence of resistant strains. In this context, key biosynthetic enzymes from Mtb are attractive targets for the development of new therapeutic drugs. Here, the 1.5 A resolution crystal structure of Mtb phosphoserine aminotransferase (MtbPSAT) in complex with its cofactor, pyridoxal 5 -phosphate (PLP), is reported. MtbPSAT is an essential enzyme in the biosynthesis of serine and in pathways of one-carbon metabolism. The structure shows that although the Mtb enzyme differs substantially in sequence from other PSAT enzymes, its fold is conserved and its PLP-binding site is virtually identical. Structural comparisons suggest that this site remains unchanged throughout the catalytic cycle. On the other hand, PSAT enzymes are obligate dimers in which the two active sites are located in the dimer interface and distinct differences in the MtbPSAT dimer are noted. These impact on the substrate-binding region and access channel and suggest options for the development of selective inhibitors.
AB - Mycobacterium tuberculosis (Mtb), the causative agent of TB, remains a serious world health problem owing to limitations of the available drugs and the emergence of resistant strains. In this context, key biosynthetic enzymes from Mtb are attractive targets for the development of new therapeutic drugs. Here, the 1.5 A resolution crystal structure of Mtb phosphoserine aminotransferase (MtbPSAT) in complex with its cofactor, pyridoxal 5 -phosphate (PLP), is reported. MtbPSAT is an essential enzyme in the biosynthesis of serine and in pathways of one-carbon metabolism. The structure shows that although the Mtb enzyme differs substantially in sequence from other PSAT enzymes, its fold is conserved and its PLP-binding site is virtually identical. Structural comparisons suggest that this site remains unchanged throughout the catalytic cycle. On the other hand, PSAT enzymes are obligate dimers in which the two active sites are located in the dimer interface and distinct differences in the MtbPSAT dimer are noted. These impact on the substrate-binding region and access channel and suggest options for the development of selective inhibitors.
UR - http://www.ncbi.nlm.nih.gov/pubmed/22525753
U2 - 10.1107/S0907444912004829
DO - 10.1107/S0907444912004829
M3 - Article
VL - 68
SP - 553
EP - 563
JO - Acta Crystallographica Section D: Structural Biology
JF - Acta Crystallographica Section D: Structural Biology
SN - 2059-7983
IS - 5
ER -