2cfb

From Proteopedia

Revision as of 16:02, 5 November 2007

GLUTAMATE-1-SEMIALDEHYDE 2,1-AMINOMUTASE FROM THERMOSYNECHOCOCCUS ELONGATUS

Overview

Glutamate-1-semialdehyde 2,1-aminomutase (GSAM) is the second enzyme in, the C(5) pathway of tetrapyrrole biosynthesis found in most bacteria, in, archaea and in plants. It catalyzes the transamination of, glutamate-1-semialdehyde to 5-aminolevulinic acid (ALA) in a pyridoxal, 5'-phosphate (PLP)-dependent manner. We present the crystal structure of, GSAM from the thermophilic cyanobacterium Thermosynechococcus elongatus, (GSAM(Tel)) in its PLP-bound form at 2.85A resolution. GSAM(Tel) is a, symmetric homodimer, whereas GSAM from Synechococcus (GSAM(Syn)) has been, described as asymmetric. The symmetry of GSAM(Tel) thus challenges the, previously proposed negative cooperativity between monomers of this, enzyme. Furthermore, GSAM(Tel) reveals an extensive flexible region at the, interface of the proposed complex of GSAM with glutamyl-tRNA reductase, (GluTR), the preceding enzyme in tetrapyrrole biosynthesis. Compared to, GSAM(Syn), the monomers of GSAM(Tel) are rotated away from each other, along the dimerization interface by 10 degrees . The associated, flexibility of GSAM may be essential for complex formation with GluTR to, occur. Unexpectedly, we find that GSAM is structurally related to, 5-aminolevulinate synthase (ALAS), the ALA-producing enzyme in the Shemin, pathway of alpha-proteobacteria and non-plant eukaryotes. This structural, relationship applies also to the corresponding subfamilies of, PLP-dependent enzymes. We thus propose that the CoA-subfamily (including, ALAS) and the aminotransferase subfamily II (including GSAM) are, evolutionarily closely related and that ALAS may thus have evolved from, GSAM.

About this Structure

2CFB is a Single protein structure of sequence from Synechococcus elongatus with PLR as ligand. Active as Glutamate-1-semialdehyde 2,1-aminomutase, with EC number 5.4.3.8 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Evolutionary relationship between initial enzymes of tetrapyrrole biosynthesis., Schulze JO, Schubert WD, Moser J, Jahn D, Heinz DW, J Mol Biol. 2006 May 19;358(5):1212-20. Epub 2006 Mar 10. PMID:16564539

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