3e2t
From Proteopedia
| Line 1: | Line 1: | ||
{{Seed}} | {{Seed}} | ||
| - | [[Image: | + | [[Image:3e2t.png|left|200px]] |
<!-- | <!-- | ||
| Line 11: | Line 11: | ||
===The catalytic domain of chicken tryptophan hydroxylase 1 with bound tryptophan=== | ===The catalytic domain of chicken tryptophan hydroxylase 1 with bound tryptophan=== | ||
| - | |||
| - | [[Tryptophan hydroxylase]] (TPH) is a mononuclear non-heme iron enzyme, which catalyzes the reaction between tryptophan, O 2, and tetrahydrobiopterin (BH<sub>4</sub>) to produce 5-hydroxytryptophan and 4a-hydroxytetrahydrobiopterin. This is the first and rate-limiting step in the biosynthesis of the neurotransmitter and hormone serotonin (5-hydroxytryptamine). We have determined the 1.9 A resolution crystal structure of the catalytic domain (Delta1-100/Delta415-445) of chicken TPH isoform 1 (TPH1) in complex with the tryptophan substrate and an iron-bound imidazole. This is the first structure of any aromatic amino acid hydroxylase with bound natural amino acid substrate. The iron coordination can be described as distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 A between the iron and the tryptophan Czeta3 atom that is hydroxylated. The binding of tryptophan and maybe the imidazole has caused the structural changes in the catalytic domain compared to the structure of the human TPH1 without tryptophan. The structure of chicken TPH1 is more compact, and the loops of residues Leu124-Asp139 and Ile367-Thr369 close around the active site. Similar structural changes are seen in the catalytic domain of phenylalanine hydroxylase (PAH) upon binding of substrate analogues norleucine and thienylalanine to the PAH.BH 4 complex. In fact, the chicken TPH1.Trp.imidazole structure resembles the PAH.BH 4.thienylalanine structure more (root-mean-square deviation for Calpha atoms of 0.90 A) than the human TPH1 structure (root-mean-square deviation of 1.47 A). | ||
| - | |||
| - | Crystal Structure of Tryptophan Hydroxylase with Bound Amino Acid Substrate., Windahl MS, Petersen CR, Christensen HE, Harris P, Biochemistry. 2008 Oct 21 | ||
| + | <!-- | ||
| + | The line below this paragraph, {{ABSTRACT_PUBMED_18937498}}, adds the Publication Abstract to the page | ||
| + | (as it appears on PubMed at http://www.pubmed.gov), where 18937498 is the PubMed ID number. | ||
| + | --> | ||
| + | {{ABSTRACT_PUBMED_18937498}} | ||
==About this Structure== | ==About this Structure== | ||
Revision as of 13:40, 6 April 2009
| |||||||||
| 3e2t, resolution 1.90Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||||
| Activity: | Tryptophan 5-monooxygenase, with EC number 1.14.16.4 | ||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
The catalytic domain of chicken tryptophan hydroxylase 1 with bound tryptophan
Tryptophan hydroxylase (TPH) is a mononuclear non-heme iron enzyme, which catalyzes the reaction between tryptophan, O 2, and tetrahydrobiopterin (BH 4) to produce 5-hydroxytryptophan and 4a-hydroxytetrahydrobiopterin. This is the first and rate-limiting step in the biosynthesis of the neurotransmitter and hormone serotonin (5-hydroxytryptamine). We have determined the 1.9 A resolution crystal structure of the catalytic domain (Delta1-100/Delta415-445) of chicken TPH isoform 1 (TPH1) in complex with the tryptophan substrate and an iron-bound imidazole. This is the first structure of any aromatic amino acid hydroxylase with bound natural amino acid substrate. The iron coordination can be described as distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 A between the iron and the tryptophan Czeta3 atom that is hydroxylated. The binding of tryptophan and maybe the imidazole has caused the structural changes in the catalytic domain compared to the structure of the human TPH1 without tryptophan. The structure of chicken TPH1 is more compact, and the loops of residues Leu124-Asp139 and Ile367-Thr369 close around the active site. Similar structural changes are seen in the catalytic domain of phenylalanine hydroxylase (PAH) upon binding of substrate analogues norleucine and thienylalanine to the PAH.BH 4 complex. In fact, the chicken TPH1.Trp.imidazole structure resembles the PAH.BH 4.thienylalanine structure more (root-mean-square deviation for Calpha atoms of 0.90 A) than the human TPH1 structure (root-mean-square deviation of 1.47 A).
Crystal Structure of Tryptophan Hydroxylase with Bound Amino Acid Substrate., Windahl MS, Petersen CR, Christensen HE, Harris P, Biochemistry. 2008 Oct 21. PMID:18937498
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3E2T is a 1 chain structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.
Reference
- Windahl MS, Petersen CR, Christensen HE, Harris P. Crystal Structure of Tryptophan Hydroxylase with Bound Amino Acid Substrate. Biochemistry. 2008 Oct 21. PMID:18937498 doi:10.1021/bi8015263
Page seeded by OCA on Wed Feb 18 05:15:45 2009
