Journal Article

PUBDB-2026-01687

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Non‐Covalent [4Fe–4S]/[2Fe] Interface in HydF Guides [FeFe]‐Hydrogenase Maturation

Caserta, G. (Corresponding author) ; Cabotaje, P. R. ; Waffo, A. T. ; Prajapat, D.DESY* ; Sergeev, I.XFEL.EU*DESY* ; Frielingsdorf, S. ; Berggren, G. (Corresponding author)

2026
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/anie.8078898

Abstract: Maturation of [FeFe]-hydrogenase depends on the HydF maturase, a [4Fe–4S]-containing scaffold protein that assembles and delivers the organometallic [2Fe] subsite of the H-cluster. Despite extensive research, the function of the HydF [4Fe–4S] cluster and its interaction with the [2Fe] cofactor remains unresolved, with conflicting evidence regarding cyanide linkage isomerism and the functional role of the cubane. Using 57Fe nuclear resonance vibrational spectroscopy in combination with selective isotopic labeling, we show that the [2Fe] subsite binds adjacent to the [4Fe–4S] cluster without forming a covalent cyanide bridge, while remaining electronically coupled. Complementary protein structure predictions support this arrangement and reconcile prior spectroscopic, mutagenesis, and structural studies. Extending this framework to earlier biosynthetic steps, additional structure predictions suggest that the [4Fe–4S] cluster contributes to assembly of the CH2–NH–CH2 bridge of the [2Fe] site via interactions with the lipoate cofactor of the aminomethyl-lipoyl H-protein, thereby positioning reactive components in proximity to the [2Fe] precursor. Together, these results provide a coherent structural and mechanistic framework for HydF function across distinct stages of H-cluster biosynthesis.

Note: online first

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Contributing Institute(s):

1. FS DOOR-User (FS DOOR-User)
2. Experimentebetreuung PETRA III (FS-PET-S)

Research Program(s):

1. 632 - Materials – Quantum, Complex and Functional Materials (POF4-632) (POF4-632)
2. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
3. FS-Proposal: I-20241074 (I-20241074) (I-20241074)
4. FS-Proposal: I-20250741 (I-20250741) (I-20250741)
5. DFG project G:(GEPRIS)390540038 - EXC 2008: Unifying Systems in Catalysis "UniSysCat" (390540038) (390540038)

Experiment(s):

1. PETRA Beamline P01 (PETRA III)

Appears in the scientific report 2026

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Database coverage:
; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; Index Chemicus ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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