Function for haloacid dehalogenase-like hydrolase domain containing 2

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Haloacid dehalogenase-like hydrolase domain containing 2 (2HO4:A,B)

Where's does the name come from?

Hydolase indicates this protein's main molecular function, hydrolase activity. /Link


Definition of hydrolase activity:

Catalysis of the hydrolysis of various bonds

e.g. C-O, C-N, C-C, phosphoric anhydride bonds, etc.


Hydolysis is a breakdown process of compounds in the body,

by replace the covalent bond with water molecule and making the product more water soluble.


Domain containing 2

Domain containing 2 are illustrating it has 2 domains.

Sequence and Secondary Structure /Link

Sequence and secondary structure.png

From the above diagram, two domains are showed separately and color in blue and purple.

Type: polypeptide(L)

Length: 259 residues

Secondary Structure: 44% helical (14 helices; 123 residues) 17% beta sheet (12 strands; 48 residues)

2HO4Aa: pdp domain 2HO4Aa (in purple)

2HO4Ab: pdp domain 2HO4Ab (in blue)


What does it mean when protein with 2 domains?

It could either be 2 binding site?

Or, more than one type of molecular function?


Mouse Genome Informatics(MGI)

We found 5 Category of Function or Process with evidence in this protein.

GO Annotations in Tabular Form/Link

Category Classification Term Evidence Inferred From Ref(s)
Molecular Function catalytic activity IEA InterPro:IPR005834 J:72247
Molecular Function hydrolase activity IEA InterPro:IPR006357 J:72247
Molecular Function hydrolase activity IEA SP_KW:KW-0378 J:60000
Molecular Function magnesium ion binding IEA SP_KW:KW-0460 J:60000
Biological Process metabolic process IEA InterPro:IPR005834,InterPro:IPR006357 J:72247
Gene Ontology Evidence Code Abbreviations:

  IC  Inferred by curator 
  IDA Inferred from direct assay 
  IEA Inferred from electronic annotation 
  IGI Inferred from genetic interaction 
  IMP Inferred from mutant phenotype 
  IPI Inferred from physical interaction 
  ISS Inferred from sequence or structural similarity 
  NAS Non-traceable author statement 
  ND  No biological data available 
  RCA Reviewed computational analysis 
  TAS Traceable author statement 

So where's the evidence from?

The evidence was done by Mammalian Orthology Load, which the information was derived from Homologene National Center for Biotechnology Information. This protein was reviewed in 2004 and record with J Number: J:90500.

The Mammalian Orthology Query Result proven, the evidence was from using both Amino acid sequence comparison and Nucleotide sequence comparison on different species. And the results shown human, mouse, rat, chimpanzee and dog all has the sequence of this protein.

/Link



Protein Data Bank (PDB)

Ligands and Prosthetic Groups

ID Name Chemical Formula Weight Ligand Link
PO4 Phosphate Ion O4 P 3- 94.971 /View
MG Magnesium Ion Mg 2+ 24.305 /View
MSE Selenomethionine C5 H11 N O2 Se 196.107 /View

PBD Biology and Chemistry Report /Link


Where does the protein mainly locate?

Genomics Institute of the Novartis Research Foundation /Link

HDHD2 at.png

The diagram illustrate the expression of protein or gene in different organisms


What are the conlcusion we can withdraw from the diagram above?

The sequence expression of the protein appears more in amygdala, cortex, hypothalamus, spinal cord, dentritic cells, T cells, B cells and lymphatic system. Which means this protein expression mainly functioning in the central nerve system and immune system.

May be


How does the protein function?

What are basis of Haloacid dehalogenase family?

Identification on Haloacid dehalogenase family on the basis of the structural similarities has been described. The HAD superfamily has similar reaction mechanism base on its structure. The basis of structural of HAD family are hydrolases contains enzymes (such as L-2-haloacid dehalogenase, epoxide hydrolase), variety of phosphatases (e.g. phosphoserine phosphatase, phosphomannomutase, phosphoglycolate phosphatase and sucrose-phosphate synthase), and the catalytic subunits (such as the P-type ATPases). The ATPases are essential for the transport of cations across biological membranes, because it contains the binding sites for ATP and Mg2, and a phosphorylation site. (/ Ridder et al.,1999)


Protein2.JPG

1. The mechanism starts with the binding of the phosphorylated substrate
   mediate by Mg2 ion. (In this diagram, the substrate is a serine residue) 
   Followed by a nucleophilic attack by one of the carboxylate oxygen atoms and 
   aspartate residue to form an acyl-phosphate intermediate.  In this point, the 
   positive charge of Mg2 ion is acting on phosphorus atom to stabilize it.  
2. The acyl-phosphate intermediate is hydrolysed by nucleophilic attack 
   of a water molecule.  
3. In agreement of formation of an oxyanion intermediate on the aspartate residue, 
   mediate by counterbalanced of the Mg2 ion, and hydrolase activity on 
   phosphorylation site, this yield phosphate and free enzyme (serine residue).

What are the functions?

A research was done in 1979, by administrating chlorpromazine at the rate of 15 milligram per kilogram to rats. By determining mitochondria of the sensomotor cortex and localize Mg-activated ATPase in the cortex, the result shown hydrolase activity increased in the brain after three hours administration. The disscussion suggest the increase of ATP-hydrolase activity in the cortex will induce depression of glycolytic and respiratory activity of the cells. And this is cause by increase of permeability of the mitochndrial membranes. (Kleshchinov et al., 1979)




Literature to read

/Identification of the Mg2+-binding site in the P-type ATPase and phosphatase members of the HAD (haloacid dehalogenase) superfamily by structural similarity to the response regulator protein CheY

/Structural Snapshots of Escherichia coli Histidinol Phosphate Phosphatase along the Reaction Pathway

http://www.springerlink.com/content/mmt8t16q20131540/


What about it's functional partners

From /STRING uses orthology information from the excellent COG database, we predicted it's functional partners.

From the result of occurrence we discover KIAA0423 annotation, which is still not available (1723 aa) is it best suit predicted Functional Partners. /Link

HDHD2 and predicted functional partner.png

The above result shows using protein sequence to compare difference species and their .

e.g. Pan troglodytes and Homo sapiens are two species highly conservatity



PO4
MG
MSE