1b66

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Current revision

6-PYRUVOYL TETRAHYDROPTERIN SYNTHASE

Structural highlights

1b66 is a 2 chain structure with sequence from Rattus rattus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PTPS_RAT Note=Deficiency leads to phenylketonuria.

Function

PTPS_RAT Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The enzyme 6-pyruvoyl tetrahydropterin synthase (PTPS) catalyses the second step in the de novo biosynthesis of tetrahydrobiopterin, the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin. The Zn and Mg-dependent reaction includes a triphosphate elimination, a stereospecific reduction of the N5-C6 double bond and the oxidation of both side-chain hydroxyl groups. The crystal structure of the inactive mutant Cys42Ala of PTPS in complex with its natural substrate dihydroneopterinetriphosphate was determined at 1.9 A resolution. Additionally, the uncomplexed enzyme was refined to 2.0 A resolution. The active site of PTPS consists of the pterin-anchoring Glu A107 neighboured by two catalytic motifs: a Zn(II) binding site and an intersubunit catalytic triad formed by Cys A42, Asp B88 and His B89. In the free enzyme the Zn(II) is in tetravalent co-ordination with three histidine ligands and a water molecule. In the complex the water is replaced by the two substrate side-chain hydroxyl groups yielding a penta-co-ordinated Zn(II) ion. The Zn(II) ion plays a crucial role in catalysis. It activates the protons of the substrate, stabilizes the intermediates and disfavours the breaking of the C1'C2' bond in the pyruvoyl side-chain. Cys A42 is activated by His B89 and Asp B88 for proton abstraction from the two different substrate side-chain atoms C1', and C2'. Replacing Ala A42 in the mutant structure by the wild-type Cys by modelling shows that the C1' and C2' substrate side-chain protons are at equal distances to Cys A42 Sgamma. The basicity of Cys A42 may be increased by a catalytic triad His B89 and Asp B88. The active site of PTPS seems to be optimised to carry out proton abstractions from two different side-chain C1' and C2' atoms, with no obvious preference for one of them. Kinetic studies with dihydroneopterin monophosphate reveal that the triphosphate moiety of the substrate is necessary for enzyme specifity.

Crystallographic and kinetic investigations on the mechanism of 6-pyruvoyl tetrahydropterin synthase.,Ploom T, Thony B, Yim J, Lee S, Nar H, Leimbacher W, Richardson J, Huber R, Auerbach G J Mol Biol. 1999 Feb 26;286(3):851-60. PMID:10024455^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ploom T, Thony B, Yim J, Lee S, Nar H, Leimbacher W, Richardson J, Huber R, Auerbach G. Crystallographic and kinetic investigations on the mechanism of 6-pyruvoyl tetrahydropterin synthase. J Mol Biol. 1999 Feb 26;286(3):851-60. PMID:10024455 doi:10.1006/jmbi.1998.2511

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1b66"

@@ Line 3: / Line 3: @@
 <StructureSection load='1b66' size='340' side='right'caption='[[1b66]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1b66]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B66 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1b66]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_rattus Rattus rattus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B66 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BIO:BIOPTERIN'>BIO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/6-pyruvoyltetrahydropterin_synthase 6-pyruvoyltetrahydropterin synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.12 4.2.3.12] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BIO:BIOPTERIN'>BIO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1b66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b66 OCA], [https://pdbe.org/1b66 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b66 RCSB], [https://www.ebi.ac.uk/pdbsum/1b66 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b66 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/PTPS_RAT PTPS_RAT]] Note=Deficiency leads to phenylketonuria.
+[https://www.uniprot.org/uniprot/PTPS_RAT PTPS_RAT] Note=Deficiency leads to phenylketonuria.
 == Function ==
-[[https://www.uniprot.org/uniprot/PTPS_RAT PTPS_RAT]] Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
+[https://www.uniprot.org/uniprot/PTPS_RAT PTPS_RAT] Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: 6-pyruvoyltetrahydropterin synthase]]
 [[Category: Large Structures]]
-[[Category: Auerbach, G]]
+[[Category: Rattus rattus]]
-[[Category: Huber, R]]
+[[Category: Auerbach G]]
-[[Category: Lee, S]]
+[[Category: Huber R]]
-[[Category: Leimbacher, W]]
+[[Category: Lee S]]
-[[Category: Nar, H]]
+[[Category: Leimbacher W]]
-[[Category: Ploom, T]]
+[[Category: Nar H]]
-[[Category: Richardson, J]]
+[[Category: Ploom T]]
-[[Category: Thoeny, B]]
+[[Category: Richardson J]]
-[[Category: Yim, J]]
+[[Category: Thoeny B]]
-[[Category: Phosphate elimination]]
+[[Category: Yim J]]
-[[Category: Pterine synthesis]]
-[[Category: Tetrahydrobiopterin biosynthesis]]

1b66

From Proteopedia

Current revision

6-PYRUVOYL TETRAHYDROPTERIN SYNTHASE

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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