Modeling and experiment yields the structure of acireductone dioxygenase from Klebsiella pneumoniae

Pochapsky, Thomas C.; Pochapsky, Susan Sondej; Ju, Tingting; Mo, Huaping; Al-Mjeni, Faizah; Maroney, Michael J.

doi:10.1038/nsb863

Cited by 97 publications

(138 citation statements)

References 38 publications

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“…While introduction of Nδ ligation of the iron at His 98 into our structural calculations for ARD′ resulted in multiple NOE violations in the active site, such a switch made little difference in calculations of Ni binding in ARD using modeled coordinates (9). It is possible that nickel prefers Nδ ligation at His 98.…”

Section: Discussionmentioning

confidence: 99%

“…In ARD, residues 39-50 form a largely disordered loop between strand D of the β-sandwich and the beginning of the E helix, with few NOEs between residues in this loop and other parts of the protein (9,12). In ARD′, however, this loop becomes more ordered, particularly those residues near the side chain of Tyr 57 on the E helix.…”

Section: A Structural Entropy Switch Between Ard and Ard′mentioning

confidence: 98%

“…It has been shown (7,8) that Ni +2 in ARD can be conservatively replaced by Mn +2 or Co +2 , giving rise to ARD activity (CO production), while Fe +2 in ARD′ can be replaced (albeit with lower activity) by Mg +2 . This promiscuity towards metal cofactors of widely different reduction potentials suggests that the metal is not an activator of triplet O 2 , but rather acts to control protein structure and ligand orientation so as to direct the reaction between O 2 and acireductone towards a particular regiochemistry (9). ARD belongs to the cupin structural superfamily.…”

Section: Introductionmentioning

confidence: 99%

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One Protein, Two Enzymes Revisited: A Structural Entropy Switch Interconverts the Two Isoforms of Acireductone Dioxygenase

Goldsmith

Chai

et al. 2006

Journal of Molecular Biology

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130

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SummaryAcireductone dioxygenase (ARD) catalyzes different reactions between O 2 and 1,2-dihydroxy-3-oxo-5-(methylthio)pent-1-ene (acireductone) depending upon the metal bound in the active site. Ni +2 -ARD cleaves acireductone to formate, CO and methylthiopropionate. If Fe +2 is bound (ARD ′), the same substrates yield methylthioketobutyrate and formate. The two forms differ in structure, and are chromatographically separable. Paramagnetism of Fe +2 renders the active site of ARD′ inaccessible to standard NMR methods. The structure of ARD′ has been determined using Fe +2 binding parameters determined by X-ray absorption spectroscopy and NMR restraints from H98S ARD, a metal-free diamagnetic protein that is isostructural with ARD′. ARD′ retains the β-sandwich fold of ARD, but a structural entropy switch increases order at one end of a two-helix system that bisects the β-sandwich and decreases order at the other upon interconversion of ARD and ARD′, causing loss of the C-terminal helix in ARD′ and rearrangements of residues involved in substrate orientation in the active site.

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Section: Discussionmentioning

confidence: 99%

Section: A Structural Entropy Switch Between Ard and Ard′mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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One Protein, Two Enzymes Revisited: A Structural Entropy Switch Interconverts the Two Isoforms of Acireductone Dioxygenase

Goldsmith

Chai

et al. 2006

Journal of Molecular Biology

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130

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“…The NMR experiments and methodology used for sequential assignment and tertiary structural determination of Ni-ARD have been described previously (Mo et al, 1999;Pochapsky et al, 2002). Determination of residual dipolar couplings was accomplished using 1 H, 15 N HSQC spectra obtained without 1 H decoupling in the indirect dimension on a Varian INOVA 14 T (600 MHz 1 H) NMR spectrometer, Quadrature detection in the indirect dimension was obtained using the Rance-Kay method (Muhandiram and Kay, 1994).…”

Section: Nmr Data Acquisition and Analysismentioning

confidence: 99%

A Refined Model for the Structure of Acireductone Dioxygenase from Klebsiella ATCC 8724 Incorporating Residual Dipolar Couplings

Pochapsky

et al. 2006

J Biomol NMR

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SummaryAcireductone dioxygenase (ARD) from Klebsiella ATCC 8724 is a metalloenzyme that is capable of catalyzing different reactions with the same substrates (acireductone and O 2 ) depending upon the metal bound in the active site. A model for the solution structure of the paramagnetic Ni 2+ -containing ARD has been refined using residual dipolar couplings (RDCs) measured in two media. Additional dihedral restraints based on chemical shift (TALOS) were included in the refinement, and backbone structure in the vicinity of the active site was modeled from a crystallographic structure of the mouse homolog of ARD. The incorporation of residual dipolar couplings into the structural refinement alters the relative orientations of several structural features significantly, and improves local secondary structure determination. Comparisons between the solution structures obtained with and without RDCs are made, and structural similarities and differences between mouse and bacterial enzymes are described. Finally, the biological significance of these differences is considered.

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“…The structure of a nickel-binding dioxygenase, acireductone dioxygenase (Ni-ARD) from Klebsiella pneumoniae, was recently determined by NMR and its active site modeled by comparative homology modeling (23). It was suggested that ARD might also be a member of the cupin superfamily.…”

Section: Resultsmentioning

confidence: 99%

Crystal Structure of Human Pirin

Pang

Bartlam

Zeng

et al. 2004

Journal of Biological Chemistry

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Pirin is a newly identified nuclear protein that interacts with the oncoprotein B-cell lymphoma 3-encoded (Bcl-3) and nuclear factor I (NFI). The crystal structure of human Pirin at 2.1-Å resolution shows it to be a member of the functionally diverse cupin superfamily. The structure comprises two ␤-barrel domains, with an Fe(II) cofactor bound within the cavity of the N-terminal domain. These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-B transcription pathway and the interaction with NFI in DNA replication. Substitution of iron by heavy metals thus provides a novel pathway for these metals to directly influence gene transcription. The structure suggests an interesting new role of iron in biology and that Pirin may be involved in novel mechanisms of gene regulation.Pirin is a newly identified nuclear protein that is widely expressed in dot-like subnuclear structures in human tissues, in particular liver and heart (1). Pirins are highly conserved among mammals, plants, fungi, and even prokaryotic organisms and have been assigned as a sub-family of the cupin superfamily based on both structure and sequence homology (1, 2). The cupin superfamily is among the most functionally diverse of any protein family described to date, with both enzymatic and non-enzymatic members included (2). This cupin superfamily is grouped according to a conserved ␤-barrel fold and two characteristic sequence motifs. Study of Pirin reveals two cupin domains from its primary sequence that are consistent with other members of the superfamily.The exact functions of Pirins are not yet known. No enzymatic activity has been described, but human Pirin has been found to bind to the nuclear factor I/CCAAT box transcription factor (NFI) 1 and to the oncoprotein B cell lymphoma 3-encoded (Bcl-3) in vivo (1, 3), suggesting that it is a transcription cofactor. NFI is known to stimulate DNA replication and RNA polymerase II-driven transcription (4). Bcl-3 is a distinctive member of the I B family, which inhibits the transcription factor NF-B by preventing NF-B nuclear translocation and DNA binding. However, there is also evidence that Bcl-3 preferentially binds to NF-B p50 or p52 homodimers to stimulate transcription (5). The functional nature of this difference between I B (inhibiting) and Bcl-3 (enhancing) is not known, but it is clear that they bind to different protein partners. Pirin is one of four binding partners of Bcl-3, together with Bard1, Tip60, and Jab1, and can be sequestered into quaternary complexes with Bcl-3, p50, and DNA (3). These four Bcl-3-interacting protein partners, which do not share any sequence homology, might play some crucial role in regulating the function of Bcl-3 and I B. Indeed, both Pirin and Bcl-3 are localized in the nucleus, and the potential roles of Pirin in NF-B-dependent transcriptional regulation are implicated i...

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Modeling and experiment yields the structure of acireductone dioxygenase from Klebsiella pneumoniae

Cited by 97 publications

References 38 publications

One Protein, Two Enzymes Revisited: A Structural Entropy Switch Interconverts the Two Isoforms of Acireductone Dioxygenase

One Protein, Two Enzymes Revisited: A Structural Entropy Switch Interconverts the Two Isoforms of Acireductone Dioxygenase

A Refined Model for the Structure of Acireductone Dioxygenase from Klebsiella ATCC 8724 Incorporating Residual Dipolar Couplings

Crystal Structure of Human Pirin

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