PDBsum entry 2fit

Chromosomal translocation

PDB id: 2fit

Contents

Protein chain

130 a.a. *

Ligands

FRU

SO4 ×2

Waters ×112

* Residue conservation analysis

PDB id:

2fit

Name:

Chromosomal translocation

Title:

Fhit (fragile histidine triad protein)

Structure:

Fragile histidine protein. Chain: a. Synonym: fhit, fragile histidine triad protein. Engineered: yes. Other_details: selenomethionyl fhit with bound sulfate in active site

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fhit. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: expressed as fusion protein with glutathione-s- transferase

Biol. unit:

Dimer (from PDB file)

Resolution:

1.90Å R-factor: 0.222 R-free: 0.249

Authors:

C.D.Lima,K.L.D'Amico,I.Naday,G.Rosenbaum,E.M.Westbrook, W.A.Hendrickson

Key ref:

C.D.Lima et al. (1997). MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family. Structure, 5, 763-774. PubMed id: 9261067 DOI: 10.1016/S0969-2126(97)00231-1

Date:

17-May-97 Release date: 19-Nov-97

Protein chain

P49789  (FHIT_HUMAN) -  Bis(5'-adenosyl)-triphosphatase from Homo sapiens

Seq: 147 a.a.

Struc: 130 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.7.51 - adenylylsulfate--ammonia adenylyltransferase.
• Reaction: adenosine 5'-phosphosulfate + NH4⁺ = adenosine 5'-phosphoramidate + sulfate + 2 H⁺

adenosine 5'-phosphosulfate + NH4(+) = adenosine 5'-phosphoramidate + sulfate + 2 × H(+) (Bound ligand (Het Group name = SO4) corresponds exactly)

• Enzyme class 3: E.C.3.6.1.29 - bis(5'-adenosyl)-triphosphatase.
• Reaction: P₁,P₃-bis(5'-adenosyl) triphosphate + H2O = AMP + ADP + 2 H⁺
• Enzyme class 4: E.C.3.6.2.1 - adenylylsulfatase.
• Reaction: adenosine 5'-phosphosulfate + H2O = sulfate + AMP + 2 H⁺

adenosine 5'-phosphosulfate + H2O = sulfate + AMP + 2 × H(+) (Bound ligand (Het Group name = SO4) corresponds exactly)

• Enzyme class 5: E.C.3.9.1.- - ?????

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(97)00231-1

Structure 5:763-774 (1997)

PubMed id: 9261067

MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family.

C.D.Lima, K.L.D'Amico, I.Naday, G.Rosenbaum, E.M.Westbrook, W.A.Hendrickson.

ABSTRACT

BACKGROUND: The fragile histidine triad (FHIT) protein is a member of the large and ubiquitous histidine triad (HIT) family of proteins. It is expressed from a gene located at a fragile site on human chromosome 3, which is commonly disrupted in association with certain cancers. On the basis of the genetic evidence, it has been postulated that the FHIT protein may function as a tumor suppressor, implying a role for the FHIT protein in carcinogenesis. The FHIT protein has dinucleoside polyphosphate hydrolase activity in vitro, thus suggesting that its role in vivo may involve the hydrolysis of a phosphoanhydride bond. The structural analysis of FHIT will identify critical residues involved in substrate binding and catalysis, and will provide insights into the in vivo function of HIT proteins. RESULTS: The three-dimensional crystal structures of free and nucleoside complexed FHIT have been determined from multiwavelength anomalous diffraction (MAD) data, and they represent some of the first successful structures to be measured with undulator radiation at the Advanced Photon Source. The structures of FHIT reveal that this protein exists as an intimate homodimer, which is based on a core structure observed previously in another human HIT homolog, protein kinase C interacting protein (PKCI), but has distinctive elaborations at both the N and C termini. Conserved residues within the HIT family, which are involved in the interactions of the proteins with nucleoside and phosphate groups, appear to be relevant for the catalytic activity of this protein. CONCLUSIONS: The structure of FHIT, a divergent HIT protein family member, in complex with a nucleotide analog suggests a metal-independent catalytic mechanism for the HIT family of proteins. A structural comparison of FHIT with PKCI and galactose-1-phosphate uridylyltransferase (GaIT) reveals additional implications for the structural and functional evolution of the ubiquitous HIT family of proteins.

Selected figure(s)

Figure 5.
Figure 5. Schematic stereo diagram of FHIT in adenosine/sulfate product complexed form. Hydrogen-bonding interactions thought to be important in catalysis and ligand recognition are depicted by dotted lines. To simplify the depiction, only a subset of residues have been shown superimposed on the Ca backbone spline. Although most residues involved in interactions between protein and adenine base are not conserved between FHIT and PKCI (not shown here), both proteins utilize a deep hydrophobic cleft and water-mediated contacts to the backbone of N-terminal residues in binding the adenosine base.

The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 763-774) copyright 1997.

Figure was selected by an automated process.