View source for 9ubs


==The structure of the AglA_T220R-Arg complex==
<StructureSection load='9ubs' size='340' side='right'caption='[[9ubs]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ubs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_monomycini Streptomyces monomycini]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9UBS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9UBS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.49&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARG:ARGININE'>ARG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=9ubs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ubs OCA], [https://pdbe.org/9ubs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ubs RCSB], [https://www.ebi.ac.uk/pdbsum/9ubs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ubs ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The YqcI/YcgG family of heme-dependent enzymes catalyzes guanidine N-H hydroxylation, a critical yet enigmatic step in bioactive natural product biosynthesis. Here, this mechanistic puzzle is resolved through high-resolution structural snapshots of AglA, a prototypical YqcI/YcgG member, revealing a non-canonical heme-binding "sandwich" fold. A dynamic regiochemical gating mechanism is uncovered: substrate-induced remodeling of loop L2 and key residues (Phe152, Arg179, Phe182) spatially constrains the guanidine group of aminomethylphosphonate-linked arginine (AMPn-Arg), enforcing exclusive internal N(epsilon) hydroxylation. Single-site mutations rewire hydrogen-bond networks to enable hydroxylation of free L-arginine with controllable regioselectivity (internal N(delta) vs terminal N(omega)) while preserving native internal N(epsilon) selectivity for AMPn-Arg. Crystal structures of engineered variants with free arginine, together with MD simulations, explain how subtle rearrangements of loop L2 and residues Phe152/Arg179/Phe182 pivot the guanidinium group relative to the heme Fe(IV) = O intermediate. Fusing AglA to its native PDR/VanB reductase yields a self-sufficient chimera with improved catalytic efficiency. This work establishes a structural blueprint for tuning guanidino N-H hydroxylation and demonstrates proof-of-principle control of regioselectivity in a non-canonical heme enzyme, thereby advancing the synthesis of arginine-based antibiotics and precision-functionalized therapeutics.

A Dynamic Gate Enables Regioselective Hydroxylation of Free Arginine by a Non-Canonical Heme Enzyme.,Sun Y, Dou C, Yan W, Chen P, Zhang L, Zhou D, Zheng Y, Long Z, Li S, Xu X, Huang Q, Zhu X, Cheng W Adv Sci (Weinh). 2025 Nov 12:e13032. doi: 10.1002/advs.202513032. PMID:41221789<ref>PMID:41221789</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9ubs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces monomycini]]
[[Category: Cheng W]]
[[Category: Dou C]]
[[Category: Sun Y]]
[[Category: Yan W]]
[[Category: Zhou D]]
[[Category: Zhu X]]