The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP.

abstract

• The crystal structure of HGPRTase with bound GMP has been determined and refined to 2.5 A resolution. The enzyme has a core alpha/beta structure resembling the nucleotide-binding fold of dehydrogenases, and a second lobe composed of residues from the amino and carboxy termini. The GMP molecule binds in an anti conformation in a solvent-exposed cleft of the enzyme. Lys-165, which forms a hydrogen bond to O6 of GMP, appears to be critical for determining the specificity for guanine and hypoxanthine over adenine. The location of active site residues also provides evidence for a possible mechanism for general base-assisted HGPRTase catalysis. A rationalization of the effects on stability and activity of naturally occurring single amino acid mutations of HGPRTase is presented, including a discussion of several mutations at the active site that lead to Lesch-Nyhan syndrome.

authors

• Sacchettini, James

published proceedings

• Cell

altmetric score

• 6

author list (cited authors)

• Eads, J. C., Scapin, G., Xu, Y., Grubmeyer, C., & Sacchettini, J. C.

citation count

• 194

complete list of authors

• Eads, JC||Scapin, G||Xu, Y||Grubmeyer, C||Sacchettini, JC

publication date

• July 1994

publisher

• Elsevier  Publisher

published in

• Cell  Journal

keywords

• Amino Acid Sequence
• Binding Sites
• Crystallography
• Crystallography, X-Ray
• Guanosine Monophosphate
• Humans
• Hypoxanthine Phosphoribosyltransferase
• Models, Molecular
• Molecular Sequence Data
• Molecular Structure
• Mutation
• Protein Conformation
• Recombinant Proteins

PubMed Central ID

• 8044844

Digital Object Identifier (DOI)

• 10.1016/0092-8674(94)90301-8

start page

• 325

end page

• 334

volume

• 78

issue

• 2

URL

• http://dx.doi.org/10.1016/0092-8674(94)90301-8