This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4mln

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal of PhnZ bound to (R)-2-amino-1-hydroxyethylphosphonic acid

Structural highlights

4mln is a 2 chain structure with sequence from Uncultured bacterium HF130_AEPn_1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PHNZ_UNCHF Involved in the degradation of the organophosphonate 2-aminoethylphosphonic acid (2-AEP) (Probable). Catalyzes the cleavage of the carbon-phosphorus bond of (2-amino-1-hydroxyethyl)phosphonic acid to yield glycine and phosphate through an oxidative mechanism (PubMed:22564006, PubMed:24198335, PubMed:24706911). It reacts stereospecifically with the R-enantiomer of (2-amino-1-hydroxyethyl)phosphonic acid and is also able to use (R,R)-2-amino-1-hydroxypropylphosphonate as substrate (PubMed:24706911).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The enzymes PhnY and PhnZ comprise an oxidative catabolic pathway that enables marine bacteria to use 2-aminoethylphosphonic acid as a source of inorganic phosphate. PhnZ is notable for catalyzing the oxidative cleavage of a carbon-phosphorus bond using Fe(II) and dioxygen, despite belonging to a large family of hydrolytic enzymes, the HD-phosphohydrolase superfamily. We have determined high-resolution structures of PhnZ bound to its substrate, (R)-2-amino-1-hydroxyethylphosphonate (2.1 A), and a buffer additive, l-tartrate (1.7 A). The structures reveal PhnZ to have an active site containing two Fe ions coordinated by four histidines and two aspartates that is strikingly similar to the carbon-carbon bond cleaving enzyme, myo-inositol-oxygenase. The exception is Y24, which forms a transient ligand interaction at the dioxygen binding site of Fe2. Site-directed mutagenesis and kinetic analysis with substrate analogs revealed the roles of key active site residues. A fifth histidine that is conserved in the PhnZ subclade, H62, specifically interacts with the substrate 1-hydroxyl. The structures also revealed that Y24 and E27 mediate a unique induced-fit mechanism whereby E27 specifically recognizes the 2-amino group of the bound substrate and toggles the release of Y24 from the active site, thereby creating space for molecular oxygen to bind to Fe2. Structural comparisons of PhnZ reveal an evolutionary connection between Fe(II)-dependent hydrolysis of phosphate esters and oxidative carbon-phosphorus or carbon-carbon bond cleavage, thus uniting the diverse chemistries that are found in the HD superfamily.

Crystal structure of PhnZ in complex with substrate reveals a di-iron oxygenase mechanism for catabolism of organophosphonates.,van Staalduinen LM, McSorley FR, Schiessl K, Seguin J, Wyatt PB, Hammerschmidt F, Zechel DL, Jia Z Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5171-6. doi:, 10.1073/pnas.1320039111. Epub 2014 Mar 21. PMID:24706911^[5]

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

References

↑ McSorley FR, Wyatt PB, Martinez A, DeLong EF, Hove-Jensen B, Zechel DL. PhnY and PhnZ comprise a new oxidative pathway for enzymatic cleavage of a carbon-phosphorus bond. J Am Chem Soc. 2012 May 23;134(20):8364-7. doi: 10.1021/ja302072f. Epub 2012 May , 11. PMID:22564006 doi:http://dx.doi.org/10.1021/ja302072f
↑ Worsdorfer B, Lingaraju M, Yennawar NH, Boal AK, Krebs C, Bollinger JM Jr, Pandelia ME. Organophosphonate-degrading PhnZ reveals an emerging family of HD domain mixed-valent diiron oxygenases. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18874-9. doi:, 10.1073/pnas.1315927110. Epub 2013 Nov 6. PMID:24198335 doi:http://dx.doi.org/10.1073/pnas.1315927110
↑ van Staalduinen LM, McSorley FR, Schiessl K, Seguin J, Wyatt PB, Hammerschmidt F, Zechel DL, Jia Z. Crystal structure of PhnZ in complex with substrate reveals a di-iron oxygenase mechanism for catabolism of organophosphonates. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5171-6. doi:, 10.1073/pnas.1320039111. Epub 2014 Mar 21. PMID:24706911 doi:http://dx.doi.org/10.1073/pnas.1320039111
↑ Martinez A, Tyson GW, Delong EF. Widespread known and novel phosphonate utilization pathways in marine bacteria revealed by functional screening and metagenomic analyses. Environ Microbiol. 2010 Jan;12(1):222-38. doi: 10.1111/j.1462-2920.2009.02062.x. , Epub 2009 Sep 29. PMID:19788654 doi:http://dx.doi.org/10.1111/j.1462-2920.2009.02062.x
↑ van Staalduinen LM, McSorley FR, Schiessl K, Seguin J, Wyatt PB, Hammerschmidt F, Zechel DL, Jia Z. Crystal structure of PhnZ in complex with substrate reveals a di-iron oxygenase mechanism for catabolism of organophosphonates. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5171-6. doi:, 10.1073/pnas.1320039111. Epub 2014 Mar 21. PMID:24706911 doi:http://dx.doi.org/10.1073/pnas.1320039111

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4mln"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4mln]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Uncultured_bacterium_HF130_AEPn_1 Uncultured bacterium HF130_AEPn_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MLN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MLN FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=ODV:[(1R)-2-AMINO-1-HYDROXYETHYL]PHOSPHONIC+ACID'>ODV</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]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=ODV:[(1R)-2-AMINO-1-HYDROXYETHYL]PHOSPHONIC+ACID'>ODV</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=4mln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mln OCA], [https://pdbe.org/4mln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mln RCSB], [https://www.ebi.ac.uk/pdbsum/4mln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mln ProSAT]</span></td></tr>
 </table>

4mln

From Proteopedia

Current revision

Crystal of PhnZ bound to (R)-2-amino-1-hydroxyethylphosphonic acid

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox