Structural highlights
4lh2 is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| Related: | 3v9l, 3v9g, 3v9h, 3v9i, 3v9j, 3v9k, 4lgz, 4lh0, 4lh1, 4lh3 |
| Gene: | ADLH4a1, Aldh4a1 (LK3 transgenic mice) |
| Activity: | 1-pyrroline-5-carboxylate dehydrogenase, with EC number 1.5.1.12 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[AL4A1_MOUSE] Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes (By similarity).
Publication Abstract from PubMed
The enzyme Delta1-pyrroline-5-carboxylate (P5C) dehydrogenase (aka P5CDH and ALDH4A1) is an aldehyde dehydrogenase that catalyzes the oxidation of gamma-glutamate semialdehyde to l-glutamate. The crystal structures of mouse P5CDH complexed with glutarate, succinate, malonate, glyoxylate, and acetate are reported. The structures are used to build a structure-activity relationship that describes the semialdehyde carbon chain length and the position of the aldehyde group in relation to the cysteine nucleophile and oxyanion hole. Efficient 4- and 5-carbon substrates share the common feature of being long enough to span the distance between the anchor loop at the bottom of the active site and the oxyanion hole at the top of the active site. The inactive 2- and 3-carbon semialdehydes bind the anchor loop but are too short to reach the oxyanion hole. Inhibition of P5CDH by glyoxylate, malonate, succinate, glutarate, and l-glutamate is also examined. The Ki values are 0.27mM for glyoxylate, 58mM for succinate, 30mM for glutarate, and 12mM for l-glutamate. Curiously, malonate is not an inhibitor. The trends in Ki likely reflect a trade-off between the penalty for desolvating the carboxylates of the free inhibitor and the number of compensating hydrogen bonds formed in the enzyme-inhibitor complex.
Structural basis of substrate selectivity of Delta-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): Semialdehyde chain length.,Pemberton TA, Tanner JJ Arch Biochem Biophys. 2013 Aug 6. pii: S0003-9861(13)00231-2. doi:, 10.1016/j.abb.2013.07.024. PMID:23928095[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pemberton TA, Tanner JJ. Structural basis of substrate selectivity of Delta-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): Semialdehyde chain length. Arch Biochem Biophys. 2013 Aug 6. pii: S0003-9861(13)00231-2. doi:, 10.1016/j.abb.2013.07.024. PMID:23928095 doi:10.1016/j.abb.2013.07.024
