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PDBsum entry 1r3a
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protein Protein-protein interface(s) links
Transferase PDB id
1r3a

 

 

 

 

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Contents
Protein chains
359 a.a.
Theoretical model
PDB id:
1r3a
Name: Transferase
Title: Theoretical model of human galactose-1-phosphate uridylyl transferase (galt)
Structure: Galactose-1-phosphate uridylyltransferase. Chain: a, b. Synonym: gal-1-p uridylyltransferase, udp-glucose--hexose- 1-phosphate uridylyltransferase. Ec: 2.7.7.12
Source: Homo sapiens. Human
Authors: A.Marabotti,A.M.Facchiano
Key ref: A.Marabotti and A.M.Facchiano (2005). Homology modeling studies on human galactose-1-phosphate uridylyltransferase and on its galactosemia-related mutant Q188R provide an explanation of molecular effects of the mutation on homo- and heterodimers. J Med Chem, 48, 773-779. PubMed id: 15689161 DOI: 10.1021/jm049731q
Date:
01-Oct-03     Release date:   07-Dec-04    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P07902  (GALT_HUMAN) -  Galactose-1-phosphate uridylyltransferase
Seq:
Struc: 		379 a.a.
359 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1021/jm049731q J Med Chem 48:773-779 (2005)
PubMed id: 15689161  
 
 
Homology modeling studies on human galactose-1-phosphate uridylyltransferase and on its galactosemia-related mutant Q188R provide an explanation of molecular effects of the mutation on homo- and heterodimers.
A.Marabotti, A.M.Facchiano.
 
  ABSTRACT  
 
We have created theoretical models of the three-dimensional dimeric structure of human galactose-1-phosphate uridylyltransferase as well as of homo- and heterodimers carrying the Q188R mutation by using comparative modeling procedures. These mutants are associated to the most frequent form of the genetic disease galactosemia. We have analyzed the impact of this mutation both on enzyme-substrate interactions as well as on interchain interactions in the heterodimers and in the homodimer. We suggest a molecular explanation for the altered function, caused by different enzyme-substrate interactions, and for the partial dominant negative effect of the mutant allele that is present in heterozygotes for this gene, related to a substantial loss of interchain hydrogen bonds. These results can be considered a starting point for a more extensive characterization at the molecular level of the other mutations linked to this genetic disease.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20008339 A.Facchiano, and A.Marabotti (2010).
Analysis of galactosemia-linked mutations of GALT enzyme using a computational biology approach.
  Protein Eng Des Sel, 23, 103-113.  
19859980 K.Lai, L.J.Elsas, and K.J.Wierenga (2009).
Galactose toxicity in animals.
  IUBMB Life, 61, 1063-1074.  
18932014 J.Zschocke (2008).
Dominant versus recessive: molecular mechanisms in metabolic disease.
  J Inherit Metab Dis, 31, 599-618.  
18355316 M.Porcelli, L.Concilio, I.Peluso, A.Marabotti, A.Facchiano, and G.Cacciapuoti (2008).
Pyrimidine-specific ribonucleoside hydrolase from the archaeon Sulfolobus solfataricus--biochemical characterization and homology modeling.
  FEBS J, 275, 1900-1914.  
16913843 A.M.Facchiano, S.Costantini, A.Di Maro, D.Panichi, A.Chambery, A.Parente, S.Di Gennaro, and E.Poerio (2006).
Modeling the 3D structure of wheat subtilisin/chymotrypsin inhibitor (WSCI). Probing the reactive site with two susceptible proteinases by time-course analysis and molecular dynamics simulations.
  Biol Chem, 387, 931-940.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.

 

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