Structural highlights
5txt is a 6 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| NonStd Res: | |
| Related: | 5txr |
| Gene: | HEM1, CYD1, YDR232W, YD9934.16 (Baker's yeast) |
| Activity: | 5-aminolevulinate synthase, with EC number 2.3.1.37 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[HEM1_YEAST] Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis.[1]
Publication Abstract from PubMed
5-Aminolevulinic acid synthase (ALAS) catalyzes the first step in heme biosynthesis. We present the crystal structure of a eukaryotic ALAS from Saccharomyces cerevisiae. In this homodimeric structure, one ALAS subunit contains covalently bound cofactor, pyridoxal 5'-phosphate (PLP), whereas the second is PLP free. Comparison between the subunits reveals PLP-coupled reordering of the active site and of additional regions to achieve the active conformation of the enzyme. The eukaryotic C-terminal extension, a region altered in multiple human disease alleles, wraps around the dimer and contacts active-site-proximal residues. Mutational analysis demonstrates that this C-terminal region that engages the active site is important for ALAS activity. Our discovery of structural elements that change conformation upon PLP binding and of direct contact between the C-terminal extension and the active site thus provides a structural basis for investigation of disruptions in the first step of heme biosynthesis and resulting human disorders.
Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme.,Brown BL, Kardon JR, Sauer RT, Baker TA Structure. 2018 Apr 3;26(4):580-589.e4. doi: 10.1016/j.str.2018.02.012. Epub 2018, Mar 15. PMID:29551290[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Volland C, Felix F. Isolation and properties of 5-aminolevulinate synthase from the yeast Saccharomyces cerevisiae. Eur J Biochem. 1984 Aug 1;142(3):551-7. PMID:6381051
- ↑ Brown BL, Kardon JR, Sauer RT, Baker TA. Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme. Structure. 2018 Apr 3;26(4):580-589.e4. doi: 10.1016/j.str.2018.02.012. Epub 2018, Mar 15. PMID:29551290 doi:http://dx.doi.org/10.1016/j.str.2018.02.012
