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metal-binding sites

Neil Clarke Neil.Clarke at qmail.bs.jhu.edu
Mon Jan 9 11:11:20 EST 1995

In article <9501041949.AA28566 at silibone.cchem.berkeley.edu>,

> We are looking for programs which search backbone structures for metal-binding
> sites--specifically, we are interested in "designing" such sites in non-metallo
> enzymes in order to improve catalysis.  Thanks in advance!

Hi, I think we've got just the thing for you - METAL-SEARCH is a program I
wrote several years ago to find tetrahedral Cys/His sites in proteins given
backbone coordinates.  Lynne Regan and I have a paper in which we describe
the properties of a designed four helix bundle protein (alpha4, the DeGrado
protein) into which we designed Cys2-His2 site (Biochem 29 10878 (1990)). 
The site shows the Co(2+) spectroscopic properties consistent with
tetrahedral binding involving two cysteines.  More recently we (Lynnes's
lab and mine) have come back to metal binding site design studies.  My lab
is interested in studying the effects of non-binding residues on a designed
site in a homeodomain.  The Regan lab has constructed a site (Cys3HIs1) in
a protein G domain that is very well behaved.  It seems to have all of the
properties we would hope to see - stable, well-ordered protein, tetrahedral
site, correct ligands involved, etc. The protein is substantially
destabilized with respect to the wt, but, hey, you can't have it all.  A
paper describing that protein has been submitted.

We are currently rewriting METAL-SEARCH for public consumption.  The
original version was fairly VAX dependent and used some subroutines from
Carl Pabo's PROTEUS subroutine library.  It was also decidedly
UNuserfriendly, both in running the program and in interpreting the output.
 We hope to have the new version ready for distribution in within the next
4-6 weeks, and also plan to improve on the program over the next few years.
Let me know if you'd like it.   

-Neil Clarke. 

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