Linked Life Data

16359702

Source:http://linkedlifedata.com/resource/pubmed/id/16359702

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-1-2
pubmed:databankReference
pubmed:abstractText
Guanosine monophosphate reductase (GMPR) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP, and plays a critical role in re-utilization of free intracellular bases and purine nucleosides. Here, we report the first crystal structure of human GMP reductase 2 (hGMPR2) in complex with GMP at 3.0 A resolution. The protein forms a tetramer composed of subunits adopting the ubiquitous (alpha/beta)8 barrel fold. Interestingly, the substrate GMP is bound to hGMPR2 through interactions with Met269, Ser270, Arg286, Ser288, and Gly290; this makes the conformation of the adjacent flexible binding region (residues 268-289) fixed, much like a door on a hinge. Structure comparison and sequence alignment analyses show that the conformation of the active site loop (residues 179-187) is similar to those of hGMPR1 and inosine monophosphate dehydrogenases (IMPDHs). We propose that Cys186 is the potential active site, and that the conformation of the loop (residues 129-133) suggests a preference for the coenzyme NADPH over NADH. This structure provides important information towards understanding the functions of members of the GMPR family.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
355
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
980-8
pubmed:dateRevised
2007-7-25
pubmed:meshHeading
pubmed-meshheading:16359702-5'-Guanylic Acid, pubmed-meshheading:16359702-Amino Acid Sequence, pubmed-meshheading:16359702-Animals, pubmed-meshheading:16359702-Binding Sites, pubmed-meshheading:16359702-Crystallography, X-Ray, pubmed-meshheading:16359702-GMP Reductase, pubmed-meshheading:16359702-Humans, pubmed-meshheading:16359702-IMP Dehydrogenase, pubmed-meshheading:16359702-Models, Molecular, pubmed-meshheading:16359702-Molecular Sequence Data, pubmed-meshheading:16359702-NADH, NADPH Oxidoreductases, pubmed-meshheading:16359702-Protein Binding, pubmed-meshheading:16359702-Protein Structure, Quaternary, pubmed-meshheading:16359702-Protein Structure, Secondary, pubmed-meshheading:16359702-Protein Subunits, pubmed-meshheading:16359702-Sequence Alignment, pubmed-meshheading:16359702-Sequence Homology, Amino Acid
pubmed:year
2006
pubmed:articleTitle
Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP.
pubmed:affiliation
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't