protein design using computational methods

William R. Pearson wrp at biochsn.acc.Virginia.EDU
Mon May 20 15:53:41 EST 1991


> sjhg9320 at uxa.cso.uiuc.edu  writes:
>wrp at biochsn.acc.Virginia.EDU (William R. Pearson) writes:
>
>>	I do not believe that there are any "well-known cases" of proteins
>>of very similar sequence (>50% identity) folding into different
>>conformations. I would be very interested in evidence to the contrary.
>
>Consider ion channels such as the Axon Na+ Channel, the proton pore of
>the V-Type ATPases, or lac permease.
>
>Scott Howard

	I have done some comparisons of lac permease (PIR code GREC) with
the sodium channel protein I of rat (PIR code A25019), and while these
two proteins do share considerable similarity (16% identity over 232
amino acids), they are certainly not >50% identical, and it is not at all
clear that the two sequences are likely to share a common ancestor;
many unrelated membrane proteins share about the same amount of
similarity.  Lac permease does not share dramatic similarity with any
other proteins in the PIR protein sequence database, with the
exception of a Klebsiella lac permease.

	So I am not clear what these sequences show. They are not >50%
identical.  I do not know whether they share similar structures.
There are plenty of examples of very distant proteins that share
considerably less than 20% sequence identity but have similar
structures.  Such proteins are usually considered homologous, since
structure is more highly conserved than sequence.

	Still awaiting "well-known" cases.

	Bill Pearson



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