3UNC

Crystal Structure of Bovine Milk Xanthine Dehydrogenase to 1.65A Resolution

Summary for 3UNC

• Entry DOI: 10.2210/pdb3unc/pdb
• Related: 1FO4 3UNA 3UNI
• Descriptor: Xanthine dehydrogenase/oxidase, FE2/S2 (INORGANIC) CLUSTER, PHOSPHONIC ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER, ... (10 entities in total)
• Functional Keywords: xanthine dehydrogenase, oxidoreductase
• Biological source: Bos taurus (bovine)
• Cellular location: Cytoplasm (By similarity): P80457
• Total number of polymer chains: 2
• Total formula weight: 300013.94

Authors

Eger, B.T.,Okamoto, K.,Nishino, T.,Pai, E.F. (deposition date: 2011-11-15, release date: 2012-05-09, Last modification date: 2023-09-13)

Primary citation

Ishikita, H.,Eger, B.T.,Okamoto, K.,Nishino, T.,Pai, E.F.
Protein conformational gating of enzymatic activity in xanthine oxidoreductase.
J.Am.Chem.Soc., 134:999-1009, 2012

PubMed Abstract: In mammals, xanthine oxidoreductase can exist as xanthine dehydrogenase (XDH) and xanthine oxidase (XO). The two enzymes possess common redox active cofactors, which form an electron transfer (ET) pathway terminated by a flavin cofactor. In spite of identical protein primary structures, the redox potential difference between XDH and XO for the flavin semiquinone/hydroquinone pair (E(sq/hq)) is ~170 mV, a striking difference. The former greatly prefers NAD(+) as ultimate substrate for ET from the iron-sulfur cluster FeS-II via flavin while the latter only accepts dioxygen. In XDH (without NAD(+)), however, the redox potential of the electron donor FeS-II is 180 mV higher than that for the acceptor flavin, yielding an energetically uphill ET. On the basis of new 1.65, 2.3, 1.9, and 2.2 Å resolution crystal structures for XDH, XO, the NAD(+)- and NADH-complexed XDH, E(sq/hq) were calculated to better understand how the enzyme activates an ET from FeS-II to flavin. The majority of the E(sq/hq) difference between XDH and XO originates from a conformational change in the loop at positions 423-433 near the flavin binding site, causing the differences in stability of the semiquinone state. There was no large conformational change observed in response to NAD(+) binding at XDH. Instead, the positive charge of the NAD(+) ring, deprotonation of Asp429, and capping of the bulk surface of the flavin by the NAD(+) molecule all contribute to altering E(sq/hq) upon NAD(+) binding to XDH.

PubMed: 22145797
DOI: 10.1021/ja207173p

Experimental method

X-RAY DIFFRACTION (1.65 Å)