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==Overview== | ==Overview== | ||
5-Aminolevulinate synthase (ALAS) is the first and rate-limiting enzyme of, heme biosynthesis in humans, animals, other non-plant eukaryotes, and, alpha-proteobacteria. It catalyzes the synthesis of 5-aminolevulinic acid, the first common precursor of all tetrapyrroles, from glycine and, succinyl-coenzyme A (sCoA) in a pyridoxal 5'-phosphate (PLP)-dependent, manner. X-linked sideroblastic anemias (XLSAs), a group of severe, disorders in humans characterized by inadequate formation of heme in, erythroblast mitochondria, are caused by mutations in the gene for, erythroid eALAS, one of two human genes for ALAS. We present the first, crystal structure of homodimeric ALAS from Rhodobacter capsulatus, (ALAS(Rc)) binding its cofactor PLP. We, furthermore, present structures, of ALAS(Rc) in ... | 5-Aminolevulinate synthase (ALAS) is the first and rate-limiting enzyme of, heme biosynthesis in humans, animals, other non-plant eukaryotes, and, alpha-proteobacteria. It catalyzes the synthesis of 5-aminolevulinic acid, the first common precursor of all tetrapyrroles, from glycine and, succinyl-coenzyme A (sCoA) in a pyridoxal 5'-phosphate (PLP)-dependent, manner. X-linked sideroblastic anemias (XLSAs), a group of severe, disorders in humans characterized by inadequate formation of heme in, erythroblast mitochondria, are caused by mutations in the gene for, erythroid eALAS, one of two human genes for ALAS. We present the first, crystal structure of homodimeric ALAS from Rhodobacter capsulatus, (ALAS(Rc)) binding its cofactor PLP. We, furthermore, present structures, of ALAS(Rc) in complex with the substrates glycine or sCoA. The sequence, identity of ALAS from R. capsulatus and human eALAS is 49%. XLSA-causing, mutations may thus be mapped, revealing the molecular basis of XLSA in, humans. Mutations are found to obstruct substrate binding, disrupt the, dimer interface, or hamper the correct folding. The structure of ALAS, completes the structural analysis of enzymes in heme biosynthesis. | ||
==About this Structure== | ==About this Structure== | ||
2BWO is a | 2BWO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rhodobacter_capsulatus Rhodobacter capsulatus] with SCA and PLP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/5-aminolevulinate_synthase 5-aminolevulinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.37 2.3.1.37] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BWO OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
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Revision as of 13:54, 5 November 2007
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5-AMINOLEVULINATE SYNTHASE FROM RHODOBACTER CAPSULATUS IN COMPLEX WITH SUCCINYL-COA
OverviewOverview
5-Aminolevulinate synthase (ALAS) is the first and rate-limiting enzyme of, heme biosynthesis in humans, animals, other non-plant eukaryotes, and, alpha-proteobacteria. It catalyzes the synthesis of 5-aminolevulinic acid, the first common precursor of all tetrapyrroles, from glycine and, succinyl-coenzyme A (sCoA) in a pyridoxal 5'-phosphate (PLP)-dependent, manner. X-linked sideroblastic anemias (XLSAs), a group of severe, disorders in humans characterized by inadequate formation of heme in, erythroblast mitochondria, are caused by mutations in the gene for, erythroid eALAS, one of two human genes for ALAS. We present the first, crystal structure of homodimeric ALAS from Rhodobacter capsulatus, (ALAS(Rc)) binding its cofactor PLP. We, furthermore, present structures, of ALAS(Rc) in complex with the substrates glycine or sCoA. The sequence, identity of ALAS from R. capsulatus and human eALAS is 49%. XLSA-causing, mutations may thus be mapped, revealing the molecular basis of XLSA in, humans. Mutations are found to obstruct substrate binding, disrupt the, dimer interface, or hamper the correct folding. The structure of ALAS, completes the structural analysis of enzymes in heme biosynthesis.
About this StructureAbout this Structure
2BWO is a Single protein structure of sequence from Rhodobacter capsulatus with SCA and PLP as ligands. Active as 5-aminolevulinate synthase, with EC number 2.3.1.37 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans., Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW, EMBO J. 2005 Sep 21;24(18):3166-77. Epub 2005 Aug 25. PMID:16121195
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