Coupled Formation of an Amidotransferase Interdomain Ammonia Channel and a Phosphoribosyltransferase Active Site
Activation of glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase (GPATase) by binding of a PRPP substrate analog results in the formation of a 20 Å channel connecting the active site for glutamine hydrolysis in one domain with the PRPP site in a second domain. This solvent-inaccessible ch...
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Published in | Biochemistry (Easton) Vol. 36; no. 37; pp. 11061 - 11068 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
16.09.1997
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Subjects | |
Online Access | Get full text |
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Summary: | Activation of glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase (GPATase) by binding of a PRPP substrate analog results in the formation of a 20 Å channel connecting the active site for glutamine hydrolysis in one domain with the PRPP site in a second domain. This solvent-inaccessible channel permits transfer of the NH3 intermediate between the two active sites. Tunneling of NH3 may be a common mechanism for glutamine amidotransferase-catalyzed nitrogen transfer and for coordination of catalysis at two distinct active sites in complex enzymes. The 2.4 Å crystal structure of the active conformer of GPATase also provides the first description of an intact active site for the phosphoribosyltransferase (PRTase) family of nucleotide synthesis and salvage enzymes. Chemical assistance to catalysis is provided primarily by the substrate and secondarily by the enzyme in the proposed structure-based mechanism. Different catalytic and inhibitory modes of divalent cation binding to the PRTase active site are revealed in the active conformer of the enzyme and in a feedback-inhibited GMP complex. |
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Bibliography: | Atomic coordinates have been deposited in the Protein Data Bank as lecc for the active conformer and lecb for the GMP-inhibited enzyme. Abstract published in Advance ACS Abstracts, August 15, 1997. ark:/67375/TPS-QZ5GNJSG-B istex:B03040C994733A995DED581DEBE8005A77144ADE Supported by NIH Grant GM-26569 and The Robert A. Welch Foundation (C-729) to R.J.P., NIH Grant GM-24658 to H.Z., and NIH Grant DK-42303 to J.L.S. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/bi9714114 |