PDBsum entry: 1nzk

Hormone/growth factor

PDB id: 1nzk

Contents

Protein chains

141 a.a. *

Ligands

SO4 ×4

FMT ×8

Waters ×437

* Residue conservation analysis

PDB id:

1nzk

Name:

Hormone/growth factor

Title:

Crystal structure of a multiple mutant (l44f, l73v, v109l, l111i, c117v) of human acidic fibroblast growth factor

Structure:

Acidic fibroblast growth factor. Chain: a, b, c, d. Synonym: heparin-binding growth factor 1. Hbgf-1. Afgf. Beta-endothelial cell growth factor. Ecgf-beta. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fgf1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.95Å R-factor: 0.196 R-free: 0.253

Authors:

S.R.Brych,J.Kim,T.M.Logan,M.Blaber

Key ref:

S.R.Brych et al. (2003). Accommodation of a highly symmetric core within a symmetric protein superfold. Protein Sci, 12, 2704-2718. PubMed id: 14627732 DOI: 10.1110/ps.03374903

Date:

18-Feb-03 Release date: 02-Mar-04

Protein chains

P05230  (FGF1_HUMAN) -  Heparin-binding growth factor 1

Seq: 155 a.a.

Struc: 141 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Biochemical function: growth factor activity (1 term)

DOI no: 10.1110/ps.03374903

Protein Sci 12:2704-2718 (2003)

PubMed id: 14627732

Accommodation of a highly symmetric core within a symmetric protein superfold.

S.R.Brych, J.Kim, T.M.Logan, M.Blaber.

ABSTRACT

An alternative core packing group, involving a set of five positions, has been introduced into human acidic FGF-1. This alternative group was designed so as to constrain the primary structure within the core region to the same threefold symmetry present in the tertiary structure of the protein fold (the beta-trefoil superfold). The alternative core is essentially indistinguishable from the WT core with regard to structure, stability, and folding kinetics. The results show that the beta-trefoil superfold is compatible with a threefold symmetric constraint on the core region, as might be the case if the superfold arose as a result of gene duplication/fusion events. Furthermore, this new core arrangement can form the basis of a structural "building block" that can greatly simplify the de novo design of beta-trefoil proteins by using symmetric structural complementarity. Remaining asymmetry within the core appears to be related to asymmetry in the tertiary structure associated with receptor and heparin binding functionality of the growth factor.

Selected figure(s)

Figure 1.
Figure 1. (Top panel) Relaxed stereo ribbon diagram (side and top views) detailing the ß-trefoil tertiary structure of FGF-1 and the associated threefold symmetry. The green color identifies the repeated structural domain. The cyan color within this domain identifies structurally conserved elements. (Middle panel) Relaxed stereo diagram showing an overlay of the three structural domains within FGF-1 (regions 11-52, 53-93, and 94-137). The overlay was performed using the structurally conserved regions (cyan color) in the top panel. (Bottom panel) Alignment of the 140-amino-acid primary structure of FGF-1 according to the threefold tertiary structure symmetry present in the ß-trefoil superfold (Murzin et al. 1992). Light gray boxes indicate residue positions with two residues in common. The dark gray box indicates the single position where all three residues are in common. The open boxes indicate the residues comprising the core packing group.

Figure 3.
Figure 3. Relaxed stereo diagram showing overlaid subdomains within WT FGF-1 (top panel) and SYM5 (bottom panel) for the core positions mutated in this study, and illustrating the symmetric rotamer orientations and packing environments for these positions.

The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 2704-2718) copyright 2003.

Figures were selected by the author.