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Cofactor mobility d...
Cofactor mobility determines reaction outcome in the IMPDH and GMPR (beta-alpha)(8) barrel enzymes
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Patton, Gregory C. (author)
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- Stenmark, Pål (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Gollapalli, Deviprasad R. (author)
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- Sevastik, Robin (author)
- Stockholms universitet,Institutionen för organisk kemi
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Kursula, Petri (author)
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Flodin, Susanne (author)
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Schuler, Herwig (author)
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Swales, Colin T. (author)
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- Eklund, Hans (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylärbiologi,Department of Molecular Biology
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- Himo, Fahmi (author)
- Stockholms universitet,Institutionen för organisk kemi
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Nordlund, Par (author)
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Hedstrom, Lizbeth (author)
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(creator_code:org_t)
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- 2011
- 2011
- English.
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In: Nature Chemical Biology. - 1552-4450 .- 1552-4469. ; 7, s. 950-958
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate reductase (GMPR) belong to the same structural family, share a common set of catalytic residues and bind the same ligands. The structural and mechanistic features that determine reaction outcome in the IMPDH and GMPR family have not been identified. Here we show that the GMPR reaction uses the same intermediate E-XMP(star) as IMPDH, but in this reaction the intermediate reacts with ammonia instead of water. A single crystal structure of human GMPR type 2 with IMP and NADPH fortuitously captures three different states, each of which mimics a distinct step in the catalytic cycle of GMPR. The cofactor is found in two conformations: an 'in' conformation poised for hydride transfer and an 'out' conformation in which the cofactor is 6 angstrom from IMP. Mutagenesis along with substrate and cofactor analog experiments demonstrate that the out conformation is required for the deamination of GMP. Remarkably, the cofactor is part of the catalytic machinery that activates ammonia.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Keyword
- Biochemistry
- biokemi
- strukturbiologi
- Structural Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Patton, Gregory ...
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Stenmark, Pål
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Gollapalli, Devi ...
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Sevastik, Robin
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Kursula, Petri
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Flodin, Susanne
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show more...
-
Schuler, Herwig
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Swales, Colin T.
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Eklund, Hans
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Himo, Fahmi
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Nordlund, Par
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Hedstrom, Lizbet ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Structural Biolo ...
- Articles in the publication
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Nature Chemical ...
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Cell Chemistry a ...
- By the university
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Stockholm University
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Swedish University of Agricultural Sciences